[{"id":"tpbg-5t4","kind":"target","name":"5T4 (trophoblast glycoprotein)","aka":["5T4","TPBG","5T4 oncofetal antigen","WAIF1"],"tldr":"A protein the placenta makes during pregnancy that many cancers switch back on while most healthy adult tissue does not. Antibody-drug conjugates against it have been tested in patients, and since 2024 the first radiolabelled versions have reached people in China.","summary":"5T4, encoded by TPBG (HGNC:12004), is a 72 kD heavily N-glycosylated membrane protein with leucine-rich repeats, first found by searching for surface molecules shared between human trophoblast and cancer cells. It is expressed by many different cancers but rarely in normal adult tissue, and its expression is linked to epithelial-mesenchymal transition, CXCL12/CXCR4 chemotaxis and a tumour-initiating phenotype (Stern and Harrop, Cancer Immunol Immunother 2017).\n\nThe target was validated clinically as an antibody-drug conjugate first. Pfizer's PF-06263507, an anti-5T4 IgG1 carrying monomethylauristatin-F, was given to 26 patients in a first-in-human trial (NCT01891669): the maximum tolerated dose was 4.34 mg/kg, ocular toxicity caused the dose-limiting events, and no objective responses were seen in patients who were not selected for 5T4 expression. In mesothelioma, 5T4 was expressed in 10 of 12 cell lines and most biopsies, and antibodies and ADCs against it internalise into lysosomes.\n\nRadiopharmaceutical work is recent and largely Chinese. A humanised single-domain antibody, [68Ga]Ga-NOTA-H006, went from camel immunisation to a pilot clinical study at Huashan Hospital, Fudan University, registered as NCT06162988, and mapped 5T4-positive lesions in patients with a mean effective dose of 0.034 mSv/MBq (EJNMMI 2025). An [18F]AlF-RESCA-H006 version was built for pancreatic adenocarcinoma, and a full-antibody theranostic pair, [89Zr]Zr-DFO-HB5 for imaging with [177Lu]Lu- and [161Tb]Tb-DOTA-HB5 for therapy, slowed tumour growth in two colorectal cancer xenograft models (J Med Chem 2026). A 2026 systematic review lists 5T4 with CEACAM5, TROP2, GPC3 and ROR1 as oncofetal surface antigens in advanced prostate cancer, including neuroendocrine and castration-resistant disease.\n\nThe open question is patient selection: the only ADC trial enrolled unselected patients and saw no responses, which is the gap a 5T4 imaging agent could close.","asOf":"2026-09-24","links":[{"label":"HGNC: TPBG gene record (HGNC:12004)","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:12004"},{"label":"He et al., EJNMMI 2025: [68Ga]Ga-NOTA-H006 preclinical and pilot clinical study (PMID 39377811)","url":"https://pubmed.ncbi.nlm.nih.gov/39377811/"},{"label":"Liang et al., J Med Chem 2026: [89Zr]Zr-DFO-HB5 immuno-PET and 161Tb vs 177Lu therapy in colorectal cancer (PMID 41984171)","url":"https://pubmed.ncbi.nlm.nih.gov/41984171/"},{"label":"Kong et al., Mol Pharm 2025: [18F]AlF-RESCA-H006 for pancreatic adenocarcinoma (PMID 40443260)","url":"https://pubmed.ncbi.nlm.nih.gov/40443260/"},{"label":"Shapiro et al., Invest New Drugs 2017: first-in-human anti-5T4 ADC PF-06263507 (PMID 28070718)","url":"https://pubmed.ncbi.nlm.nih.gov/28070718/"},{"label":"Harbi et al., EJNMMI Res 2026: oncofetal surface antigens in prostate cancer and radioligand targeting (PMID 41832388)","url":"https://pubmed.ncbi.nlm.nih.gov/41832388/"},{"label":"ClinicalTrials.gov NCT06162988: PET imaging of 68Ga-NOTA-H006 in malignancy","url":"https://clinicaltrials.gov/study/NCT06162988"}],"tags":["oncofetal antigen","antibody target","ADC-validated","China"],"related":["immuno-pet","zr-89","lu-177","tb-161","ga-68","radioligand-therapy","trop2","ceacam5","gpc3","f-18"],"indications":["colorectal-cancer","pancreatic-cancer","prostate-mcrpc","prostate-nepc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"TPBG","biology":"A heavily glycosylated leucine-rich-repeat membrane protein shared by trophoblast and cancer cells. It favours non-canonical over canonical Wnt signalling, potentiates CXCL12/CXCR4 chemotaxis and marks cells moving through epithelial-mesenchymal transition, and antibodies bound to it are internalised to lysosomes.","whereFound":["Placental trophoblast: the tissue in which it was discovered","Many carcinomas, including colorectal, pancreatic, lung and breast, with low expression in most normal adult tissue","Mesothelioma: 10 of 12 cell lines and most biopsy specimens positive, with variable intensity","Advanced prostate cancer, including neuroendocrine and castration-resistant forms (systematic review 2026)"],"targetClass":"surface-antigen","prevalence":[]},{"id":"alpha-synuclein","kind":"target","name":"Alpha-synuclein","aka":["a-synuclein","SNCA","alpha synuclein aggregates"],"tldr":"The protein that clumps inside brain cells in Parkinson's disease and related conditions. Nobody can yet see those clumps in a living person, which is why these diseases are still diagnosed by watching the patient.","summary":"Alpha-synuclein is a small presynaptic protein whose misfolded, aggregated forms define the synucleinopathies: Parkinson's disease, dementia with Lewy bodies and multiple system atrophy. Unlike amyloid and tau, which both have approved PET agents, no small molecule targeting misfolded alpha-synuclein has been approved by the FDA as a PET radiopharmaceutical, and the inability to quantify these aggregates in vivo limits accurate clinical diagnosis across the whole group.\n\nThe target is hard for physical reasons. The aggregates are intracellular and, in Parkinson's disease, present at far lower density than cortical amyloid plaques, and the protein has several conformational strains. The most advanced tracer, [18F]ACI-12589 from AC Immune, demonstrated this precisely in a 42-participant study published in Nature Communications in 2023: binding statistically separated multiple system atrophy patients from healthy controls and from other neurodegenerative disorders, with clear signal in cerebellar white matter and middle cerebellar peduncles, but showed limited binding in Parkinson's disease despite binding post-mortem Parkinson's tissue.\n\nThe competing measurement has already succeeded. Seed amplification assays on cerebrospinal fluid are reported at 87.7% sensitivity and 96.3% specificity for Parkinson's disease in the PPMI cohort, with a pooled meta-analysis across biomatrices at 0.86 and 0.92. What those assays cannot do is localise or quantify pathology, or measure whether a drug reduced it, and they are markedly less reliable in multiple system atrophy. That residual is where an imaging agent would have to earn its place.","asOf":"2026-09-23","links":[{"label":"[18F]ACI-12589 first-in-human, Nature Communications 2023","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10611796/"},{"label":"No approved small-molecule alpha-synuclein PET agent","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13121216/"},{"label":"Alpha-synuclein cannot currently be assessed accurately in vivo","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8466155/"},{"label":"Seed amplification assays: past, present and future roles","url":"https://www.movementdisorders.org/MDS/Scientific-Issues/posts/The-past-present-and-future-roles-of-a-synuclein-seed-amplification-assays.htm"},{"label":"Conference report: PET signal only in multiple system atrophy","url":"https://www.alzforum.org/news/conference-coverage/first-field-synuclein-pet-only-multiple-system-atrophy"}],"tags":["neurology","protein aggregate","unmet need"],"related":["tau-protein","amyloid-beta","opp-alpha-synuclein-pet-parkinsons","f-18"],"indications":["parkinsonian-syndromes"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"SNCA","hgnc":"HGNC:11138","ensembl":"ENSG00000145335","uniprot":"P37840","entrez":"6622","biology":"A 140-amino-acid presynaptic protein involved in vesicle trafficking, which misfolds into beta-sheet-rich oligomers and fibrils that accumulate as Lewy bodies in neurons or as glial cytoplasmic inclusions in multiple system atrophy. The aggregates are intracellular, conformationally heterogeneous and, in Parkinson's disease, present at low density.","whereFound":["Parkinson's disease: Lewy bodies and Lewy neurites in neurons","Dementia with Lewy bodies: cortical Lewy pathology","Multiple system atrophy: glial cytoplasmic inclusions, the one form a tracer has so far detected in vivo","Not a cancer target; the imaging rationale is neurological"],"targetClass":"other","prevalence":[]},{"id":"amyloid-beta","kind":"target","name":"Amyloid beta plaques","aka":["Aβ","beta-amyloid neuritic plaques"],"tldr":"Sticky clumps of protein that build up in the brain in Alzheimer's disease. PET scans using tracers that bind these clumps can show a doctor how much amyloid is present, well before it would show up on a brain biopsy.","summary":"Amyloid beta is a peptide, cleaved from the amyloid precursor protein, that misfolds and aggregates into extracellular neuritic plaques, one of the two neuropathological hallmarks of Alzheimer's disease (the other being tau neurofibrillary tangles). PET tracers such as 18F-florbetapir bind fibrillar amyloid aggregates with nanomolar affinity (Kd approximately 3.7 nM for florbetapir) and do not appreciably bind tau, so they read out plaque burden rather than tangle burden.\n\nFlorbetapir (Amyvid) was FDA-approved in 2012 for PET imaging to estimate beta-amyloid neuritic plaque density in adults with cognitive impairment being evaluated for Alzheimer's disease; its label was updated in June 2025 to add selection of patients for amyloid-targeting therapy, reflecting the arrival of anti-amyloid antibody drugs whose eligibility and monitoring depend on amyloid PET or blood biomarkers. Other approved 18F amyloid tracers include florbetaben (Neuraceq) and flutemetamol (Vizamyl); all three are stilbene or benzothiazole derivatives related to the original 11C-Pittsburgh compound B.\n\nAs an imaging target, amyloid's strength is that a negative scan has high negative predictive value (sparse or no plaque makes an Alzheimer's diagnosis unlikely), which is clinically decisive. Its main limitation is specificity for a diagnosis: a positive scan indicates plaque is present but this can also occur in cognitively normal older adults and in other neurodegenerative conditions, so a positive result does not by itself confirm Alzheimer's disease, and none of the approved tracers is validated to monitor treatment response or to predict conversion to dementia.","asOf":"2026-09-22","links":[{"label":"FDA label: Amyvid (florbetapir F 18 injection)","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202008s000lbl.pdf"},{"label":"Eli Lilly: FDA approves updated Amyvid label for amyloid-targeting therapy selection (25 June 2025)","url":"https://investor.lilly.com/news-releases/news-release-details/fda-approves-updated-label-lillys-amyvid-florbetapir-f-18"},{"label":"PMC: the role of amyloid PET in imaging neurodegenerative disorders","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9165727/"},{"label":"CMS national coverage determination memo: beta-amyloid PET in dementia","url":"https://www.cms.gov/medicare-coverage-database/view/ncacal-decision-memo.aspx?proposed=N&NCAId=265"}],"tags":["neurology","Alzheimer's disease","protein aggregate"],"related":["tau-protein","f-18","c-11"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"biology":"A peptide cleaved from the amyloid precursor protein that misfolds and aggregates into extracellular neuritic plaques, one of the two defining pathologies of Alzheimer's disease. PET tracers bind fibrillar amyloid aggregates with high affinity, giving an in-vivo readout of plaque burden that was previously only obtainable at autopsy.","whereFound":["Alzheimer's disease: neuritic plaques throughout association cortex; presence and density scored on amyloid PET","Cognitively normal older adults: a minority show plaque on amyloid PET without dementia","Cerebral amyloid angiopathy and some other neurodegenerative conditions: variable vascular and parenchymal amyloid"],"targetClass":"other","prevalence":[]},{"id":"b7h3","kind":"target","name":"B7-H3","aka":[],"tldr":"B7-H3 is an immune checkpoint-like surface protein found on 60 to 70% of small-cell lung cancers and 80 to 90% of castration-resistant prostate cancers, with little on normal tissue. It is used as an ADC address, chiefly by ifinatamab deruxtecan, now in phase 3 in small-cell lung cancer; whether blocking its immune-dampening role adds anything beyond payload delivery is unresolved.","summary":"B7-H3 (CD276) is an immune checkpoint-like molecule broadly overexpressed in solid tumours with limited normal expression; its function is debated, inhibiting T-cell activation and promoting tumour cell migration. Expression is more homogeneous than many ADC targets, found in 60-70% of small-cell lung cancer and 80-90% of castration-resistant prostate cancer by IHC, as well as head and neck and paediatric solid tumours. Ifinatamab deruxtecan (I-DXd) has shown high response rates in small-cell lung cancer and is in phase 3. B7-H3 is also pursued with radioligands and CAR-T. Whether its immune-dampening role means antibodies against it add an immunological benefit beyond payload delivery is unresolved. The simple version is a widely present tumour surface protein now used mainly as an address for ADCs.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/CD276","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/CD276"}],"tags":["adc-target"],"related":[],"indications":["sclc","prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"CD276","hgnc":"HGNC:19137","ensembl":"ENSG00000103855","uniprot":"Q5ZPR3","entrez":"80381","biology":"Function debated: inhibits T-cell activation, promotes tumour cell migration. Expression is more homogeneous than many ADC targets.","whereFound":["Small-cell lung cancer","Prostate","Head and neck","Paediatric solid tumours"],"targetClass":"surface-antigen","prevalence":[{"indicationId":"sclc","pct":"60-70","measure":"IHC, any expression","source":"https://en.wikipedia.org/wiki/CD276"},{"indicationId":"prostate","pct":"80-90","measure":"IHC, any expression","source":"https://en.wikipedia.org/wiki/CD276","note":"Castration-resistant disease"}]},{"id":"bone-hydroxyapatite","kind":"target","name":"Bone mineral (hydroxyapatite)","aka":["Hydroxyapatite","bone mineral matrix"],"tldr":"The hard mineral that makes up bone. Certain radioactive drugs stick to this mineral wherever bone is being actively rebuilt, which is how bone scans find fractures, infection and cancer that has spread to bone, and how some treatments deliver radiation straight to bone metastases.","summary":"Bone is a composite of collagen protein and hydroxyapatite, a crystalline calcium phosphate mineral (Ca5(PO4)3OH). Bisphosphonates - and the older diphosphonates such as methylene diphosphonate (MDP) and hydroxymethylene diphosphonate (HDP/HMDP) - bind hydroxyapatite with high affinity through a P-C-P backbone that chelates surface calcium ions in a bidentate arrangement; when labelled with technetium-99m, the resulting Tc-99m-MDP or Tc-99m-HDP complex accumulates on bone in proportion to local blood flow and osteoblastic activity (new bone formation provides more, smaller hydroxyapatite crystals with greater surface area for binding), which is the basis of conventional bone scintigraphy.\n\nA related but chemically distinct mechanism is direct ionic exchange: 18F-fluoride ions substitute for hydroxyl groups in the hydroxyapatite lattice to form fluoroapatite, giving even faster, higher-contrast bone-turnover imaging on PET than Tc-99m bone scans. On the therapy side, the same hydroxyapatite affinity is exploited by bone-seeking radionuclide therapies: samarium-153 lexidronam (a Sm-153-EDTMP bisphosphonate complex) and radium-223 dichloride (a calcium mimetic incorporated directly into the mineral at sites of osteoblastic activity) both concentrate in areas of high bone turnover, including osteoblastic bone metastases, to deliver localised radiation for pain palliation or, for radium-223, a survival benefit in castration-resistant prostate cancer with bone metastases.\n\nAs a target, hydroxyapatite's strength is that bone-turnover tracers and therapies go wherever remodelling is happening, with no receptor saturation or internalisation step required (bone-seeking agents work by chemisorption or ionic exchange, not receptor binding). Its central weakness is a lack of disease specificity: fractures, arthritis, Paget's disease and infection all increase osteoblastic activity and light up alongside malignancy, so bone scans are sensitive but not specific, and specificity depends entirely on the clinical and radiological context.","asOf":"2026-09-22","links":[{"label":"StatPearls: bone scan (mechanism of Tc-99m MDP/HDP binding to hydroxyapatite)","url":"https://www.ncbi.nlm.nih.gov/books/NBK531486/"},{"label":"MDPI: bisphosphonates as radiopharmaceuticals - DOTAZOL review of bone-targeting chemistry","url":"https://www.mdpi.com/1422-0067/25/1/462"},{"label":"Applied Radiation and Isotopes review: targeted delivery to bone using bisphosphonate ligands","url":"https://ame.nd.edu/research-legacy/faculty-research-labs/rroeder/publications/publication-pdf/2016%20ADDR%20Cole.pdf"},{"label":"JNM: kinetics of bone-seeking radiotracers (Tc-99m-diphosphonate vs 18F-fluoride)","url":"https://jnm.snmjournals.org/content/jnumed/early/2013/03/11/jnumed.112.114298.full.pdf"}],"tags":["bone","mineral","palliation"],"related":["samarium-153-lexidronam","radium-223","phosphorus-32","spect","bone-metastases","f-18","tc-99m","ra-223","sm-153"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"biology":"The crystalline calcium phosphate mineral phase of bone, bound to a collagen matrix. Bisphosphonates and fluoride ions bind or exchange with this mineral at sites of active bone turnover through chemisorption or ionic substitution respectively, concentrating radiotracers or radionuclide therapy wherever bone remodelling, including reactive new bone at metastases, is occurring.","whereFound":["Sites of active bone remodelling generally: fractures, degenerative and inflammatory bone disease, Paget's disease, infection","Osteoblastic bone metastases (prostate, breast and other cancers): increased uptake reflecting reactive new bone formation","Normal growing skeleton: high uptake at epiphyseal growth plates and osteochondral junctions"],"targetClass":"other","prevalence":[]},{"id":"bradykinin-b1-receptor","kind":"target","name":"Bradykinin B1 receptor (B1R)","aka":["B1R","BDKRB1","BKR1","B1BKR"],"tldr":"A receptor that healthy tissue barely makes but inflammation and many cancers switch on. Gallium-68 and fluorine-18 peptides built from B1R-blocking drugs give sharp PET images in mice, but no B1R tracer has been given to a patient.","summary":"The bradykinin B1 receptor, encoded by BDKRB1 (HGNC:1029), is a G-protein-coupled receptor that is overexpressed in a variety of cancers while being essentially absent from healthy tissue, which is what first drew imaging groups to it.\n\nMost of the published radiochemistry comes from BC Cancer in Vancouver. In a 2015 Journal of Nuclear Medicine study, three gallium-68-labelled peptides derived from the B1R antagonists B9858 and B9958 bound the receptor with nanomolar affinity (Ki 1.1 to 16.0 nM), cleared through the kidneys, and at one hour showed only kidneys, bladder and B1R-positive tumours on PET; the best, 68Ga-P04158 and 68Ga-Z02090, reached 19.6 and 14.4% injected dose per gram in tumour. The same group then made 68Ga- and 18F-labelled derivatives of the more peptidase-stable antagonist R954, with tumour uptake around 8.5 to 9.3% injected dose per gram at one hour. Those studies used cells engineered to express human B1R. In 2024 a Showa Pharmaceutical University group showed that an indium-111 R954 derivative also tracks B1R expressed naturally in glioblastoma cells, with uptake that followed B1R levels and was blocked by unlabelled R954.\n\nA search of ClinicalTrials.gov on 24 September 2026 found no registered B1R imaging or therapy trial. The gaps are a first-in-human study and evidence of which human tumours carry enough receptor to image or treat.","asOf":"2026-09-24","links":[{"label":"HGNC: BDKRB1 gene record (HGNC:1029)","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:1029"},{"label":"Lin et al., J Nucl Med 2015: three 68Ga-labelled [des-Arg10]kallidin derivatives for B1R PET (PMID 25745086)","url":"https://pubmed.ncbi.nlm.nih.gov/25745086/"},{"label":"Kuo et al., Mol Pharm 2017: 68Ga- and 18F-labelled R954 derivatives for B1R PET (PMID 28094956)","url":"https://pubmed.ncbi.nlm.nih.gov/28094956/"},{"label":"Shukuri et al., Pharmaceuticals 2024: 111In-R954 derivative detects endogenous B1R in glioblastoma xenografts (PMID 39065752)","url":"https://pubmed.ncbi.nlm.nih.gov/39065752/"}],"tags":["GPCR","peptide receptor","preclinical only","unmet need"],"related":["ga-68","f-18","in-111","pet","glioblastoma","grpr"],"indications":["glioblastoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"BDKRB1","biology":"An inducible G-protein-coupled receptor for des-Arg kinins. It is barely expressed in healthy tissue but upregulated by inflammation and in many tumours, and antagonist peptides such as B9858, B9958 and R954 bind it with nanomolar affinity, which is the basis of the radiolabelled derivatives.","whereFound":["A variety of cancers, with limited or no expression in healthy tissue (BC Cancer radiochemistry series)","Glioblastoma cell lines: U87MG expresses more than U251MG, and radiotracer uptake follows that difference","Inflamed tissue, where expression is induced"],"targetClass":"other","prevalence":[]},{"id":"caix","kind":"target","name":"CAIX (carbonic anhydrase IX)","aka":["CA9","G250 antigen","MN antigen"],"tldr":"A protein that clear cell kidney cancer makes almost all the time because of a gene fault. It helps the tumour survive in low-oxygen conditions, and antibodies that stick to it can be used to find or treat the cancer.","summary":"Carbonic anhydrase IX is a transmembrane enzyme with an extracellular catalytic domain that helps regulate intracellular and extracellular pH, allowing tumour cells to survive an acidic, hypoxic microenvironment. Its expression is switched on by the HIF-1 transcription factor: in clear cell renal cell carcinoma (ccRCC), loss-of-function mutation or deletion of the VHL tumour-suppressor gene (found in roughly 75-95% of ccRCC cases) leaves HIF-1α constitutively active even without hypoxia, so CAIX is expressed diffusely and strongly on almost all ccRCC cells, in contrast to normal kidney, which does not express it.\n\nThis expression pattern (near-ubiquitous in ccRCC, essentially absent in normal renal parenchyma and in non-clear-cell kidney tumours) is what makes CAIX attractive: it is a differential diagnostic marker for ccRCC as well as a therapeutic target. The chimeric monoclonal antibody girentuximab (cG250) binds a conformational epitope on the catalytic domain, internalises via clathrin-coated vesicles and recycles rather than being degraded, giving long intracellular retention. Because girentuximab is a full antibody, tumour-to-background contrast builds slowly and imaging is typically read several days after injection.\n\nAs a target, CAIX's strength is its consistency and specificity in ccRCC; its weakness for antibody-based approaches is slow pharmacokinetics (days, not hours) and the fact that HIF-2α-driven, VHL-independent disease later in progression can show falling CAIX expression, which has been linked to worse prognosis. Small-molecule and peptide CAIX ligands (for example 68Ga-DPI-4452) have since been developed to give same-day imaging with high tumour-to-background contrast.","asOf":"2026-09-22","links":[{"label":"PMC review: CAIX in renal cell carcinoma, implications for imaging and therapy","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7582814/"},{"label":"PMC: application of CAIX-targeted radiotracers in ccRCC","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12976585/"},{"label":"Spandidos: monoclonal antibody G250 targeting CAIX, internalisation and epitope","url":"https://www.spandidos-publications.com/10.3892/ijo.2014.2658/download"},{"label":"JNM editorial: kick-starting molecular theranostics in renal cell carcinoma (VHL/HIF, girentuximab, 68Ga-DPI-4452)","url":"https://jnm.snmjournals.org/content/65/5/744"}],"tags":["renal cell carcinoma","hypoxia","antibody target"],"related":["girentuximab-zr89","caix-pet","rcc","hif-vhl","idea-caix-theranostics","nct06750419","nct07197580","telix","ga-68"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"CA9","biology":"A transmembrane carbonic anhydrase whose extracellular catalytic domain hydrates CO2 to bicarbonate and protons, helping tumour cells regulate pH and survive hypoxia. Its expression is switched on by the HIF-1 pathway, so it is expressed at very high, uniform density in VHL-mutant clear cell renal cell carcinoma while normal kidney does not express it.","whereFound":["Clear cell renal cell carcinoma: overexpressed in >90-95% of cases, driven by VHL/HIF-1 pathway loss","Normal kidney parenchyma: essentially absent","Some hypoxic non-renal tumours (expression follows tumour hypoxia rather than a fixed tissue pattern)","Normal gastrointestinal tract: low-level physiological expression"],"targetClass":"enzyme","prevalence":[]},{"id":"cck2-receptor","kind":"target","name":"CCK2 receptor (gastrin receptor)","aka":["CCK2R","CCK-B receptor","gastrin receptor"],"tldr":"A docking site for the hormone gastrin, found at very high numbers on medullary thyroid cancer cells. Minigastrin-like radioactive drugs can bind it to find or treat that cancer, though they also light up the stomach because the same receptor lines it normally.","summary":"CCK2R is a G-protein-coupled receptor for the hormones gastrin and cholecystokinin, expressed physiologically in the gastric mucosa where it regulates acid secretion, and in parts of the central nervous system. It is overexpressed at very high incidence and density in medullary thyroid carcinoma (MTC) - historically detected indirectly through the pentagastrin stimulation test - and also occurs in a substantial minority of small-cell lung cancers, astrocytomas, stromal ovarian cancers, gastrointestinal stromal tumours and some gastroenteropancreatic neuroendocrine tumours.\n\nRadiolabelled analogues of minigastrin, which retains the C-terminal receptor-binding tetrapeptide sequence (Trp-Met-Asp-Phe-NH2) common to gastrin and CCK, have been developed for both imaging (111In-, 99mTc-, or 68Ga-labelled minigastrin analogues, including Demogastrin 2 and MGS5) and therapy (90Y- or 177Lu-labelled minigastrin, such as 177Lu-PP-F11N). In patients with metastatic MTC, CCK2R-targeted imaging has detected more lesions than somatostatin receptor imaging, reflecting the low SSTR expression typical of MTC.\n\nAs a target, CCK2R's strength is very high density (over 90% of MTCs) and no competing standard-of-care radiotracer. Its central weakness, which has so far limited therapeutic use, is that the stomach expresses CCK2R physiologically and receives a comparable or higher radiation dose than the tumour with agonist-based minigastrin analogues, making the stomach dose-limiting; kidney and bone-marrow toxicity have also constrained early therapy trials, and receptor antagonist-based ligands (for example those built on nastorazepide) are being explored as an alternative with potentially better tumour-to-stomach ratios.","asOf":"2026-09-22","links":[{"label":"PMC: radiolabeled CCK/gastrin peptides for imaging and therapy","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC3205271/"},{"label":"JNM: CCK2 receptor agonist 177Lu-PP-F11N for medullary thyroid carcinoma therapy - dosimetry","url":"https://jnm.snmjournals.org/content/61/4/520"},{"label":"PMC: cholecystokinin-2 receptor targeting with radiolabeled peptides (review)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7116483/"},{"label":"Theranostics: nastorazepide-based CCK2R antagonist radioligands","url":"https://www.thno.org/v16p8447.htm"}],"tags":["neuroendocrine","thyroid","GPCR"],"related":["thyroid","sclc","ga-68","tc-99m","in-111","lu-177","y-90"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"biology":"A G-protein-coupled receptor for gastrin and cholecystokinin that physiologically regulates gastric acid secretion. It is overexpressed at very high density in medullary thyroid carcinoma and in a substantial minority of small-cell lung cancer, astrocytoma and other tumours, providing a target for minigastrin-based radiopeptides.","whereFound":["Medullary thyroid carcinoma: expressed at high density in over 90% of cases","Small-cell lung cancer: expressed in roughly half of cases","Astrocytoma, stromal ovarian cancer, gastrointestinal stromal tumours, some gastroenteropancreatic neuroendocrine tumours: variable expression","Normal gastric mucosa: physiological expression, the dose-limiting normal-tissue site for minigastrin therapy"],"targetClass":"surface-antigen","prevalence":[]},{"id":"cd20","kind":"target","name":"CD20","aka":[],"tldr":"CD20 is a B-cell marker; rituximab against it was the first antibody approved for cancer, in 1997.","summary":"CD20 (MS4A1) is a B-cell tetraspanin that regulates calcium flux; it is not internalised, which favours effector-based antibodies and T-cell engagers over ADCs, and it is present on over 95% of DLBCL and, more dimly, over 90% of CLL. It is the target of rituximab, the first antibody approved for cancer in 1997, and of obinutuzumab. The CD20×CD3 bispecifics glofitamab, epcoritamab, mosunetuzumab, and odronextamab now offer off-the-shelf T-cell redirection in lymphoma without the manufacturing wait of CAR-T. Loss of CD20 expression is a recognised escape route after repeated anti-CD20 therapy, and the best sequencing of bispecifics versus CAR-T is still being worked out. The simple version is the B-cell marker that started antibody therapy for cancer and now anchors the newest T-cell engagers.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/CD20","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/CD20"}],"tags":["antibody-target"],"related":[],"indications":["dlbcl"],"sections":[],"technologies":[],"targets":[],"drugs":["ibritumomab-tiuxetan"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"MS4A1","hgnc":"HGNC:7315","ensembl":"ENSG00000156738","uniprot":"P11836","entrez":"931","biology":"CD20 is a tetraspanin regulating B-cell calcium flux; it is not internalised, favouring effector-based antibodies over ADCs.","whereFound":["DLBCL","Follicular lymphoma","CLL","Mantle cell lymphoma"],"targetClass":"surface-antigen","prevalence":[{"indicationId":"dlbcl","pct":">95","measure":"Surface expression","source":"https://en.wikipedia.org/wiki/CD20"}]},{"id":"ceacam5","kind":"target","name":"CEACAM5","aka":[],"tldr":"The classic 'CEA' tumour marker measured in blood, also present on the cell surface where ADCs can reach it.","summary":"CEACAM5 is carcinoembryonic antigen, a GPI-anchored adhesion molecule that is shed into circulation as the serum CEA marker and also sits on the cell surface where ADCs and T-cell engagers can reach it. It is overexpressed in colorectal (80-90% moderate-to-high by IHC), gastric (50-60%), lung adenocarcinoma, and pancreatic cancers; only 20-25% of non-squamous NSCLC met the high-expression threshold used in CARMEN. Tusamitamab ravtansine failed in phase 3 NSCLC (CARMEN-LC03), a setback that raised questions about payload choice and patient selection rather than the target itself. CEACAM5 remains pursued with T-cell engagers and next-generation ADCs. The simple version is the classic CEA blood marker, now also being used as a surface target for drug delivery.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Carcinoembryonic_antigen","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Carcinoembryonic_antigen"}],"tags":["adc-target","biomarker"],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"CEACAM5","hgnc":"HGNC:1817","ensembl":"ENSG00000105388","uniprot":"P06731","entrez":"1048","biology":"GPI-anchored adhesion molecule; shed into circulation as the serum CEA marker.","whereFound":["Colorectal","Gastric","Lung adenocarcinoma","Pancreatic"],"targetClass":"surface-antigen","prevalence":[]},{"id":"cldn18-2","kind":"target","name":"Claudin-18.2","aka":["CLDN18.2","claudin 18 isoform 2","CLDN18"],"tldr":"A protein that seals the gaps between stomach lining cells. It stays on many stomach cancers as they spread, and two approved treatments are given only to patients whose biopsy shows it.","summary":"Claudin-18 splice variant 2 is a tight-junction protein of the gastric mucosa whose epitope becomes accessible on tumour cells as normal tissue architecture breaks down, making it an unusually tractable target in a cancer with few. It is the selection biomarker for zolbetuximab, approved in the US, EU, Japan and China for CLDN18.2-positive, HER2-negative gastric and gastro-oesophageal junction adenocarcinoma, and in June 2026 China approved satricabtagene autoleucel, a CLDN18.2 CAR-T, in the same biomarker-defined population.\n\nPositivity depends entirely on where the threshold is set. Across 4,507 patients screened for the SPOTLIGHT and GLOW trials, 38.4% were positive at the label threshold of moderate-to-strong membranous staining in at least 75% of tumour cells, and the sponsor reports approximately 35% positivity in Chinese patients with advanced disease. Selection is performed with the VENTANA CLDN18 (43-14A) RxDx assay.\n\nThe assay's failure mode is sampling, and it has been quantified. Against whole-tumour-section ground truth a single representative biopsy gave 58.8% sensitivity, rising to 76.5% with six to eight biopsies, and a minimum of six endoscopic biopsies was needed to keep false negatives acceptably low; 18% of tumours were discordant between the primary and a matched nodal metastasis. A multi-laboratory ring trial found a 12% false-negative rate at 91% overall accuracy. That is the gap three Chinese groups are now trying to close with PET: 68Ga-PMD22, 68Ga-NC-BCH and 124I-18B10(10L) each have a published first-in-human pilot of 11 to 17 patients.","asOf":"2026-09-23","links":[{"label":"CLDN18.2 positivity across pooled SPOTLIGHT and GLOW screening","url":"https://link.springer.com/article/10.1007/s10120-024-01518-1"},{"label":"Single-biopsy sensitivity against whole-section truth, Scientific Reports 2025","url":"https://www.nature.com/articles/s41598-025-12337-4"},{"label":"Multi-laboratory ring trial of CLDN18.2 immunohistochemistry","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12647276/"},{"label":"First-in-human CLDN18.2 PET imaging","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11149600/"},{"label":"Gastric cancer biomarker testing review, naming the approved companion assay","url":"https://www.cancerbiomed.org/content/22/3/212"}],"tags":["adc-target","car-t-target","companion diagnostic","gastric"],"related":["opp-cldn18-2-imaging-gastric","her2","ga-68","i-124"],"indications":["gastric-oesophageal-cancer"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"CLDN18","hgnc":"HGNC:2039","ensembl":"ENSG00000066405","uniprot":"P56856","entrez":"51208","biology":"A tight-junction protein restricted to gastric mucosa in healthy tissue, whose extracellular loop becomes exposed on malignant cells when epithelial polarity is lost. Expression is retained in metastases often enough to make it a systemic therapeutic target.","whereFound":["Gastric and gastro-oesophageal junction adenocarcinoma: 38.4% positive at the 75%-of-cells threshold across 4,507 screened patients","Pancreatic adenocarcinoma, at lower frequency","Normal gastric mucosa, where the epitope is not accessible to antibodies"],"targetClass":"surface-antigen","prevalence":[{"indicationId":"gastric-oesophageal-cancer","pct":"38.4","measure":"moderate-to-strong membranous staining in at least 75% of tumour cells, pooled SPOTLIGHT and GLOW screening","source":"https://link.springer.com/article/10.1007/s10120-024-01518-1"}]},{"id":"cxcr4","kind":"target","name":"CXCR4","aka":[],"tldr":"A chemokine receptor that anchors blood cells in the marrow and helps cancer cells home to it; mutated in a third of Waldenström patients and targeted by plerixafor for stem-cell mobilisation.","summary":"CXCR4 binds CXCL12 (SDF-1) to retain haematopoietic stem cells in the marrow niche and guides metastasis of solid tumours to bone. Plerixafor (2008) blocks it to mobilise stem cells for autologous transplant; motixafortide (2023) does the same in myeloma. WHIM-like CXCR4 mutations in ~30-40% of Waldenström macroglobulinaemia slow BTK-inhibitor response; mavorixafor is in trials. CXCR4 is also imaged with Ga-68 pentixafor and treated with Lu-177 pentixather in marginal zone lymphoma and myeloma (theranostic, experimental). Balixafortide and ulocuplumab failed in solid tumours.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/CXCR4","links":[{"label":"CXCR4 in WM (Blood 2014)","url":"https://doi.org/10.1182/blood-2014-01-550905"}],"tags":["gap-fill"],"related":["ga-68","lu-177"],"indications":[],"sections":[],"technologies":["radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["theranostics"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"CXCR4","hgnc":"HGNC:2561","ensembl":"ENSG00000121966","uniprot":"P61073","entrez":"7852","biology":"G-protein-coupled receptor; CXCL12 binding activates Gαi, PI3K/AKT and MAPK, promoting chemotaxis, survival and retention in stromal niches; truncating C-terminal mutations impair receptor internalisation (WHIM syndrome).","whereFound":["Waldenström macroglobulinaemia (30-40% mutation)","Myeloma, lymphoma, AML (expression)","Breast, prostate and other solid tumours (metastatic homing)"],"targetClass":"other","prevalence":[]},{"id":"dlg4-psd95","kind":"target","name":"DLG4 (PSD-95)","aka":["PSD-95","PSD95","SAP90","postsynaptic density protein 95","DLG4"],"tldr":"The main scaffold protein on the receiving side of brain synapses. Losing synapses tracks memory decline in Alzheimer's disease, but today's synapse PET scans only see the sending side (SV2A). No tracer for PSD-95 has been published, so the receiving side cannot yet be imaged.","summary":"DLG4 (HGNC:2903) encodes postsynaptic density protein 95, the scaffold that anchors glutamate receptors in the postsynaptic density of excitatory synapses. Synapse loss is an early event in Alzheimer's disease and is closely linked to cognitive decline, and PSD-95 is one of the proteins that falls. In post-mortem brain from the Banner Sun Health Research Institute, PSD-95 was lower in every region studied in Alzheimer's dementia than in controls without dementia (not significant in the hippocampus), and PSD-95 levels correlated with tangle and plaque density and with Mini Mental State Examination scores. In cerebrospinal fluid, a Massachusetts General Hospital study of two cohorts (178 and 156 people) found PSD-95 raised in Alzheimer's disease but not specific to it.\n\nSynaptic density PET today images the presynaptic vesicle protein SV2A with tracers such as 11C-UCB-J, used for example to follow synapse loss in animal models. A PubMed search on 24 September 2026 for PSD-95 or DLG4 together with PET, SPECT, radioligand or radiotracer returned 17 records, and none described a radioligand that binds PSD-95 itself.\n\nThat absence is the point of this record. PSD-95 is an intracellular scaffold rather than a receptor, so a tracer would need to cross the blood-brain barrier and the cell membrane and bind a protein-protein interaction domain, which is harder than binding a vesicle protein. The unmet need is a postsynaptic counterpart to SV2A PET that could separate loss of receiving sites from loss of transmitting sites.","asOf":"2026-09-24","links":[{"label":"HGNC: DLG4 gene record (HGNC:2903)","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:2903"},{"label":"Serrano et al., Int J Mol Sci 2024: presynaptic and postsynaptic proteins against pathology in Alzheimer's disease (PMID 38542104)","url":"https://pubmed.ncbi.nlm.nih.gov/38542104/"},{"label":"Kivisäkk et al., Alzheimers Res Ther 2022: PSD-95, SNAP-25 and neurogranin in CSF (PMID 35461266)","url":"https://pubmed.ncbi.nlm.nih.gov/35461266/"},{"label":"PubMed search used for the absence statement: PSD-95/DLG4 with PET, SPECT, radioligand or radiotracer","url":"https://pubmed.ncbi.nlm.nih.gov/?term=%28%22PSD-95%22%5Btiab%5D+OR+PSD95%5Btiab%5D+OR+DLG4%5Btiab%5D%29+AND+%28PET%5Btiab%5D+OR+radioligand%5Btiab%5D+OR+radiotracer%5Btiab%5D+OR+radiolabeled%5Btiab%5D+OR+radiolabelled%5Btiab%5D+OR+SPECT%5Btiab%5D%29"}],"tags":["neurology","synaptic density","no tracer yet","unmet need"],"related":["alzheimers-disease","amyloid-beta","tau-protein","pet","c-11"],"indications":["alzheimers-disease"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"DLG4","biology":"A membrane-associated guanylate kinase scaffold in the postsynaptic density of excitatory synapses. Its PDZ domains bind NMDA-receptor subunits and other partners, so its level is a proxy for the number of postsynaptic sites.","whereFound":["Excitatory synapses throughout the brain, concentrated in the postsynaptic density","Reduced across cortical regions in Alzheimer's dementia in post-mortem brain","Detectable in cerebrospinal fluid, raised in Alzheimer's disease and in some inflammatory, vascular and other neurodegenerative conditions"],"targetClass":"other","prevalence":[]},{"id":"dll3","kind":"target","name":"DLL3","aka":[],"tldr":"A protein that appears on the surface of small-cell lung cancer cells, now hit by a drug that pulls T cells onto them.","summary":"Delta-like ligand 3 is an inhibitory Notch ligand aberrantly surface-expressed in ~85% of small-cell lung cancer and neuroendocrine prostate cancer. The first DLL3 ADC (rovalpituzumab tesirine) failed; the T-cell engager tarlatamab (Imdelltra) succeeded, with a survival benefit in second-line SCLC (DeLLphi-304). Trispecifics and CAR-T follow. For radiopharmaceuticals it is a target in waiting rather than in use: no DLL3 radioligand is in the clinic, and the nearest commitment is the discovery-stage DLL3 programme Telix acquired from ImaginAb in January 2025, which carries no candidate code or isotope. A surface antigen present on most small-cell lung cancers, in a disease where a scan-then-treat pair does not yet exist, is the obvious place for one.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/DLL3","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/DLL3"}],"tags":["t-cell-engager-target"],"related":[],"indications":["sclc","prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["abdera-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"DLL3","hgnc":"HGNC:2909","ensembl":"ENSG00000090932","uniprot":"Q9NYJ7","entrez":"10683","biology":"Normally intracellular Golgi protein; ASCL1-driven neuroendocrine lineage exposes it on the membrane.","whereFound":["Small-cell lung cancer","Neuroendocrine prostate cancer","Large-cell neuroendocrine carcinoma"],"targetClass":"surface-antigen","prevalence":[{"indicationId":"sclc","pct":"80-85","measure":"IHC, any expression","source":"https://en.wikipedia.org/wiki/DLL3"},{"indicationId":"prostate","pct":"70-80","measure":"Neuroendocrine prostate cancer only","source":"https://en.wikipedia.org/wiki/DLL3","note":"Rare in adenocarcinoma"}]},{"id":"dopamine-transporter","kind":"target","name":"Dopamine transporter (DAT)","aka":["DAT"],"tldr":"A protein on the ends of brain cells that make dopamine, which recycles the dopamine after it has done its job. A scan using a tracer that sticks to this protein can show whether those brain cells are dying, which happens in Parkinson's disease.","summary":"The dopamine transporter sits on the axon terminals of presynaptic nigrostriatal dopaminergic neurons, which project from the substantia nigra to the striatum (caudate and putamen), and terminates dopaminergic signalling by taking dopamine back into the neuron after release. Because DAT density on the neuron surface tracks the number of intact nigrostriatal terminals, loss of DAT signal on imaging is a marker of neurodegeneration rather than a direct marker of disease-specific pathology.\n\nIoflupane I-123 (DaTscan/DATSCAN), a radioiodinated cocaine analogue, binds reversibly to DAT (Ki approximately 0.62 nM) and is imaged by SPECT 3-6 hours after injection, concentrating in the striatum in proportion to transporter density. It is FDA- and EMA-approved as an adjunct for striatal DAT visualisation in adults with suspected parkinsonian syndromes and suspected dementia with Lewy bodies, chiefly to help distinguish essential tremor (normal DAT scan) from Parkinsonian syndromes (reduced striatal DAT), and probable dementia with Lewy bodies from Alzheimer's disease.\n\nAs a target, DAT's strength is a clean anatomical readout (striatal uptake) that reliably separates presynaptic neurodegeneration from tremor of other causes. Its main limitation is lack of specificity between the parkinsonian syndromes themselves: DaTscan cannot distinguish idiopathic Parkinson's disease from multiple system atrophy or progressive supranuclear palsy, since all three cause nigrostriatal terminal loss. A range of common drugs (stimulants, some antidepressants, benztropine) bind DAT with high affinity and can interfere with image interpretation, so they typically need to be stopped before scanning.","asOf":"2026-09-22","links":[{"label":"FDA label: DATSCAN (ioflupane I 123 injection)","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/022454s010lbl.pdf"},{"label":"FDA medical review, NDA 022454 (mechanism of action)","url":"https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022454sOrig1s000MedR.pdf"},{"label":"PMC: clinical utility of dopamine transporter SPECT imaging","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC3812862/"}],"tags":["neurology","Parkinson's disease","transporter"],"related":["i-123"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"SLC6A3","biology":"A presynaptic membrane transporter on nigrostriatal dopaminergic neuron terminals that recycles dopamine after synaptic release. Its density in the striatum reflects the number of intact dopaminergic terminals, so loss of transporter signal is a marker of the neurodegeneration that occurs in Parkinsonian syndromes and dementia with Lewy bodies.","whereFound":["Substantia nigra pars compacta neuron terminals in the striatum: high physiological expression, lost with nigrostriatal degeneration","Parkinson's disease, multiple system atrophy, progressive supranuclear palsy: reduced striatal DAT signal (not distinguishable from each other by DAT imaging alone)","Essential tremor and dementia unrelated to Lewy body disease: normal DAT signal, used to rule out parkinsonian degeneration"],"targetClass":"other","prevalence":[]},{"id":"fap","kind":"target","name":"FAP","aka":[],"tldr":"FAP (fibroblast activation protein) sits on the cancer-associated fibroblasts that scaffold more than 90% of epithelial cancers and is almost absent from normal adult tissue. FAPI PET tracers therefore light up tumours with high contrast, including pancreatic, gastric and low-grade cancers where FDG PET is weak, and FAP-targeted radioligands are in development.","summary":"Fibroblast activation protein is expressed on cancer-associated fibroblasts in >90% of epithelial cancers, with minimal expression in normal adult tissue. FAPI PET tracers (68Ga-FAPI-46, 18F-FAPI-74) offer high tumour-to-background contrast, including in cancers where FDG is weak (pancreatic, gastric, low-grade). FAP-targeted radioligands (177Lu/225Ac-FAP-2286) are in development.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Fibroblast_activation_protein,_alpha","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Fibroblast_activation_protein,_alpha"}],"tags":["theranostic","pet-target","stroma"],"related":["f-18","ga-68","lu-177","ac-225"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["ratio-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"FAP","hgnc":"HGNC:3590","ensembl":"ENSG00000078098","uniprot":"Q12884","entrez":"2191","biology":"Serine protease on activated fibroblasts; a stromal target rather than a tumour-cell target, so it is pan-cancer but does not report on the malignant cell itself.","whereFound":["Pancreatic","Gastric","Breast","Sarcoma","Almost all desmoplastic tumours"],"targetClass":"stroma","prevalence":[]},{"id":"folr1","kind":"target","name":"Folate receptor alpha","aka":[],"tldr":"Folate receptor alpha is a vitamin receptor that ovarian cancer cells carry in large numbers, used as the docking site for the ADC mirvetuximab.","summary":"FRα is overexpressed in high-grade serous ovarian cancer, endometrial cancer, and lung adenocarcinoma. Mirvetuximab soravtansine (Elahere) is approved in FRα-high platinum-resistant ovarian cancer (MIRASOL). Next-generation FRα ADCs with topoisomerase-I payloads (ZW191, luveltamab tazevibulin, rinatabart sesutecan) target lower-expressing tumours.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Folate_receptor_1","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Folate_receptor_1"}],"tags":["adc-target"],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"FOLR1","hgnc":"HGNC:3791","ensembl":"ENSG00000110195","uniprot":"P15328","entrez":"2348","biology":"GPI-anchored folate transporter; limited to apical surfaces in normal kidney, lung, and choroid plexus.","whereFound":["High-grade serous ovarian (~80% any expression)","Endometrial","NSCLC adenocarcinoma","TNBC (subset)"],"targetClass":"surface-antigen","prevalence":[]},{"id":"glut-hexokinase","kind":"target","name":"GLUT1 / hexokinase (glucose metabolism)","aka":["GLUT1","SLC2A1","hexokinase II","HK2"],"tldr":"The two-step system cells use to pull in and lock up glucose for energy. Many cancers rely on this system much more heavily than normal tissue, and a radioactive sugar look-alike called FDG exploits it to light up tumours on a PET scan.","summary":"Glucose enters cells through facilitative glucose transporters (GLUTs), of which GLUT1 is the most widely distributed, and is then immediately phosphorylated by hexokinase (chiefly hexokinase II, HK2, in tumours) to glucose-6-phosphate, trapping it inside the cell for glycolysis. Malignant cells characteristically upregulate both GLUT1 and HK2 to sustain the Warburg effect - a high rate of glycolysis even when oxygen is available, driven by oncogenic signalling (PI3K/AKT, MYC, RAS, loss of p53) and by hypoxia acting through HIF-1α, which transcriptionally activates GLUT1 and glycolytic enzymes.\n\n18F-fludeoxyglucose (FDG) is a glucose analogue that is carried into cells by GLUT1 (and GLUT3) exactly as glucose is, and phosphorylated by hexokinase to FDG-6-phosphate; because this metabolite lacks the 2'-hydroxyl group needed for further glycolytic processing and most tumours have low glucose-6-phosphatase activity to reverse the reaction, FDG-6-phosphate becomes metabolically trapped and accumulates in proportion to glycolytic flux. This is read out on PET as the standardised uptake value (SUV), the basis of FDG-PET staging, restaging and treatment response assessment across most solid tumours and lymphomas.\n\nAs a target, GLUT1/hexokinase's strength is near-universal upregulation across a very wide range of cancers, giving FDG-PET its broad utility as a single default oncology tracer. Its central weakness is specificity: any tissue with high glucose demand - brain, myocardium, active skeletal muscle, brown fat, healing wounds, infection and inflammation - also accumulates FDG strongly, so a positive scan requires anatomical and clinical correlation rather than being cancer-specific by itself; hyperglycaemia at the time of injection also competes with FDG uptake and reduces sensitivity.","asOf":"2026-09-22","links":[{"label":"PMC: roles of GLUT-1 and HK-II expression in tumour biology and FDG uptake","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6508962/"},{"label":"PMC: mechanisms underlying FDG uptake in cancer","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5120247/"},{"label":"StatPearls: fludeoxyglucose (18F) mechanism of action","url":"https://www.ncbi.nlm.nih.gov/books/NBK557653/"},{"label":"PMC: imaging cancer metabolism, underlying biology and pitfalls of FDG-PET","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6126440/"}],"tags":["metabolism","glycolysis","pan-cancer"],"related":["fludeoxyglucose-f18","fdg-pet","suv","f-18"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"SLC2A1","biology":"Glucose enters cells through facilitative glucose transporters (chiefly GLUT1) and is then phosphorylated by hexokinase (chiefly hexokinase II in tumours), trapping it inside the cell. Cancer cells characteristically upregulate both proteins to sustain high glycolytic flux even in the presence of oxygen (the Warburg effect), which is what the glucose analogue FDG exploits for PET imaging.","whereFound":["Most solid tumours and lymphomas: GLUT1 and hexokinase II upregulated in proportion to glycolytic rate, the basis of FDG-PET","Brain (grey matter), myocardium, active skeletal muscle, brown adipose tissue: high physiological glucose uptake, a source of false-positive or confounding FDG signal","Sites of infection and inflammation: activated leukocytes also take up FDG avidly, another source of non-specific uptake"],"targetClass":"enzyme","prevalence":[]},{"id":"gpc3","kind":"target","name":"Glypican-3","aka":[],"tldr":"Glypican-3 is a fetal liver protein that reappears in liver cancer, giving CAR-T and bispecifics a clean target.","summary":"Glypican-3 is a heparan sulfate proteoglycan that modulates Wnt and Hedgehog signalling; it is a fetal liver protein expressed in 70-80% of hepatocellular carcinoma and essentially absent from normal adult liver, which gives cell and bispecific therapies a clean target. It is also found in hepatoblastoma and yolk-sac tumours. Antibodies failed as monotherapy (codrituzumab), suggesting that simply binding GPC3 is not enough. GPC3 CAR-T, including armoured constructs from AstraZeneca/Neogene and Chinese groups, and GPC3×CD3 bispecifics are showing responses, though durability and the hostile liver microenvironment remain concerns. The simple version is a liver-development protein that reappears in liver cancer, letting engineered immune cells recognise the tumour.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Glypican_3","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Glypican_3"}],"tags":["car-t-target"],"related":[],"indications":["hcc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"GPC3","hgnc":"HGNC:4451","ensembl":"ENSG00000147257","uniprot":"P51654","entrez":"2719","biology":"Glypican-3 is a heparan sulfate proteoglycan modulating Wnt and Hedgehog signalling.","whereFound":["Hepatocellular carcinoma","Hepatoblastoma","Yolk-sac tumours"],"targetClass":"surface-antigen","prevalence":[{"indicationId":"hcc","pct":"70-80","measure":"IHC, any expression","source":"https://en.wikipedia.org/wiki/Glypican_3"}]},{"id":"grpr","kind":"target","name":"GRPR (gastrin-releasing peptide receptor)","aka":[],"tldr":"GRPR is a hormone receptor abundant in early and hormone-sensitive prostate cancer, imaged and treated with bombesin-like radioligands.","summary":"The gastrin-releasing peptide receptor (GRPR) is a G-protein-coupled receptor for bombesin and GRP whose expression is high in hormone-sensitive prostate cancer and falls with castration resistance. It is overexpressed in primary and hormone-naive prostate cancer, often in PSMA-negative tumours, as well as in ER-positive breast cancer and GIST, which makes it a complementary theranostic target to PSMA. Bombesin-like radioligands exploit it: 68Ga-RM2 PET for imaging and 177Lu-NeoB (Novartis) for therapy are in clinical trials. Because expression declines as disease becomes castration-resistant, GRPR agents may suit earlier disease or PSMA-negative patients rather than replacing PSMA therapy. A newcomer can think of GRPR as a second radioactive address on prostate cancer, useful where PSMA is dim.","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/Gastrin-releasing_peptide_receptor","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Gastrin-releasing_peptide_receptor"}],"tags":["theranostic"],"related":["ga-68","lu-177"],"indications":["prostate"],"sections":[],"technologies":["radioligand-therapy","pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"GRPR","hgnc":"HGNC:4609","ensembl":"ENSG00000126010","uniprot":"P30550","entrez":"2925","biology":"G-protein-coupled receptor for bombesin/GRP; expression falls with castration resistance.","whereFound":["Hormone-sensitive prostate cancer","ER+ breast cancer","GIST"],"targetClass":"surface-antigen","prevalence":[{"indicationId":"prostate","pct":100,"measure":"Receptor autoradiography, GRPR in 30 of 30 invasive prostate carcinomas","source":"https://pubmed.ncbi.nlm.nih.gov/10070977/","note":"Markwalder and Reubi 1999 (Cancer Res); receptor density was high in carcinoma and PIN and low or absent in normal and hyperplastic prostate"}]},{"id":"her2","kind":"target","name":"HER2","aka":[],"tldr":"A growth-signal receptor. Some cancers make far too much of it, and drugs that block it or use it as a docking site have transformed those cancers.","summary":"Human epidermal growth factor receptor 2 is a receptor tyrosine kinase amplified in ~15-20% of breast cancers and a subset of gastric, colorectal, lung (mutations), and biliary cancers. Trastuzumab (1998) was the first targeted antibody in solid tumours. Trastuzumab deruxtecan redefined the target by working in 'HER2-low' tumours that older drugs ignored, and in 2026 gained approval in early-stage disease.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/HER2/neu","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/HER2/neu"}],"tags":["adc-target","driver"],"related":[],"indications":["breast-her2-positive"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["precirix"],"institutions":[],"pathways":[],"terms":[],"trials":["nct06369831"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"ERBB2","hgnc":"HGNC:3430","ensembl":"ENSG00000141736","uniprot":"P04626","entrez":"2064","biology":"Ligand-less receptor that heterodimerises with HER3/EGFR to drive PI3K and MAPK signalling. Amplification is a true oncogenic driver; low expression is merely a delivery address for ADCs.","whereFound":["HER2+ breast cancer (~15-20%)","HER2-low breast cancer (~50%)","Gastric/GEJ (~15-20%)","HER2-mutant NSCLC (~2-3%)","Colorectal (~3-5%)","Biliary tract"],"targetClass":"surface-antigen","prevalence":[{"indicationId":"breast-her2-positive","pct":100,"measure":"IHC 3+ or ISH-amplified (defining)","source":"https://www.nature.com/articles/s41591-025-03981-4"}]},{"id":"her3","kind":"target","name":"HER3 (ERBB3)","aka":["ERBB3","erb-b2 receptor tyrosine kinase 3"],"tldr":"A receptor on the surface of most lung cancer cells that helps tumours resist treatment. Drugs aimed at it exist, but measuring how much of it a tumour carries has so far failed to predict who benefits.","summary":"HER3 is a member of the epidermal growth factor receptor family with impaired intrinsic kinase activity, signalling instead through heterodimerisation with HER2 and EGFR and driving the PI3K-AKT pathway. It is widely expressed in epithelial cancers and is upregulated after EGFR tyrosine-kinase inhibitor treatment, which is why it became a target for antibody-drug conjugates in EGFR-mutant lung cancer. One published series reported HER3 expression in 83% of non-small cell lung cancers, with overexpression in 42% of a 45-patient cohort, more often than HER2.\n\nThe target's problem is measurement, not prevalence. Reviews state that there are no validated HER3 immunohistochemistry assays and no standardised scoring thresholds for predicting benefit, and the sponsor's own biomarker analyses of patritumab deruxtecan report no relationship between efficacy and HER3 protein expression by immunohistochemistry. An mRNA-based alternative developed by the SOLTI group found activity across a wide range of ERBB3 expression, again suggesting limited predictive value.\n\nFor molecular imaging this matters directly. Three antibody PET tracers have been built against HER3 (64Cu-patritumab, 89Zr-GSK2849330 and 89Zr-lumretuzumab) and all three belong to therapeutic programmes that were discontinued or lost momentum; in one published study no correlation between tumour uptake and ex-vivo immunohistochemistry could be determined. A single imaging trial is currently recruiting, 89Zr-patritumab deruxtecan at the Netherlands Cancer Institute with Daiichi Sankyo, on the rationale that HER3 expression can be assessed non-invasively including at sites that are difficult to biopsy.","asOf":"2026-09-23","links":[{"label":"HER3 expression in non-small cell lung cancer","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12393064/"},{"label":"No relationship between HER3-DXd efficacy and HER3 immunohistochemistry, Nature Communications 2024","url":"https://www.nature.com/articles/s41467-024-50056-y"},{"label":"No validated HER3 assays or scoring thresholds (review)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12758208/"},{"label":"NCT06222489: 89Zr-patritumab deruxtecan PET/CT","url":"https://clinicaltrials.gov/study/NCT06222489"}],"tags":["adc-target","resistance","lung"],"related":["her2","opp-her3-imaging-crossover","cu-64","zr-89"],"indications":["nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"ERBB3","hgnc":"HGNC:3431","ensembl":"ENSG00000065361","uniprot":"P21860","entrez":"2065","biology":"A receptor tyrosine kinase of the EGFR family with negligible intrinsic catalytic activity, which signals by heterodimerising with HER2 or EGFR to activate PI3K-AKT. Its expression rises after EGFR inhibition, making it a mechanism of acquired resistance as well as a target.","whereFound":["Non-small cell lung cancer: reported in 83% of cases, with overexpression in 42% of one 45-patient cohort","Breast cancer, including after endocrine and HER2-directed therapy","Colorectal and other epithelial cancers","Upregulated in tumours progressing on EGFR tyrosine-kinase inhibitors"],"targetClass":"surface-antigen","prevalence":[{"indicationId":"nsclc","pct":83,"measure":"immunohistochemistry, any expression, published series","source":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12393064/"}]},{"id":"integrin-avb3","kind":"target","name":"Integrin αvβ3","aka":["Integrin alpha-v beta-3","vitronectin receptor"],"tldr":"A docking protein on the surface of cells that are building new blood vessels, including the blood vessels a growing tumour needs. Peptides that mimic the docking sequence (RGD) can be radiolabelled to see where this new blood-vessel growth, or the tumour cells themselves, are most active.","summary":"Integrin αvβ3 is a heterodimeric transmembrane adhesion receptor that binds extracellular matrix proteins - vitronectin, fibronectin, fibrinogen - through their exposed arginine-glycine-aspartate (RGD) amino acid motif. It is minimally expressed on quiescent, resting blood vessel endothelium but becomes strongly upregulated on activated endothelial cells during angiogenesis, where it is required for the migration, survival and maturation of newly forming vessels, and it is also directly overexpressed on the tumour cells themselves in a range of solid cancers (including glioma, melanoma and some carcinomas), where it promotes invasion and metastasis.\n\nRadiolabelled cyclic RGD peptides (starting with 18F-Galacto-RGD, the first tracer used in patients, and followed by 68Ga-, 64Cu- and 99mTc-labelled RGD monomers, dimers and tetramers) bind αvβ3 and have been used in PET and SPECT imaging as a non-invasive biomarker of tumour angiogenesis, for patient selection ahead of anti-angiogenic therapy and for monitoring treatment response. Multimeric RGD constructs improve binding avidity through a polyvalency effect and show higher, more persistent tumour uptake than monomeric RGD.\n\nAs a target, αvβ3's strength is its sharp induction on angiogenic endothelium, giving genuine biological contrast between growing and quiescent vasculature. Its central weakness for imaging purposes is that αvβ3 is not exclusively expressed on new tumour vessels - it is also present on the tumour cells, on macrophages, and in non-malignant angiogenic settings such as atherosclerotic plaque and post-infarction myocardium - so a static PET signal cannot on its own distinguish tumour-cell expression from vascular expression, and genetic knockout studies suggest angiogenesis can still proceed without αvβ3, which has limited the target's use as a stand-alone therapeutic target despite active imaging interest.","asOf":"2026-09-22","links":[{"label":"PMC: PET imaging of integrin αvβ3 expression","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC3086612/"},{"label":"PMC: clinical application of radiolabeled RGD peptides for PET imaging of angiogenesis","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4679356/"},{"label":"PMC: RGD-binding integrins revisited - review of imaging targets including αvβ3","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8038522/"},{"label":"PMC: PET radiopharmaceuticals for imaging integrin expression","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4072020/"}],"tags":["angiogenesis","integrin","RGD peptide"],"related":["f-18","ga-68","tc-99m","cu-64"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"biology":"A heterodimeric transmembrane adhesion receptor that binds RGD-motif extracellular matrix proteins such as vitronectin and fibronectin. It is minimally expressed on quiescent blood vessels but strongly upregulated on activated endothelial cells during tumour angiogenesis, and is also directly overexpressed on some tumour cells, where it promotes invasion and migration.","whereFound":["Tumour neovasculature (activated endothelial cells during angiogenesis): strongly upregulated versus quiescent vessels","Tumour cells directly in glioma, melanoma and some carcinomas: overexpression linked to invasion and metastasis","Atherosclerotic plaque and post-myocardial-infarction myocardium: upregulated on macrophages and activated endothelium, a non-oncological imaging application","Quiescent normal vasculature: low or absent expression"],"targetClass":"surface-antigen","prevalence":[]},{"id":"klk2","kind":"target","name":"KLK2 (kallikrein-2)","aka":[],"tldr":"A relative of PSA that stays attached to prostate cancer cells, used as a T-cell engager address by J&J.","summary":"Human kallikrein-2 (KLK2) is an androgen-regulated serine protease that activates PSA; unlike PSA it is retained on the prostate cell membrane, which makes it a usable address for cell-surface therapies. Expression is nearly universal in prostate cancer and prostate-restricted elsewhere, so a KLK2-directed drug can engage T cells against the tumour with little on-target damage to other tissues. The lead agent is Johnson & Johnson's pasritamig (JNJ-78278343, a KLK2 x CD3 bispecific), which showed low cytokine release and PSA responses in phase 1 and is in phase 3 (KLK2-P3-01) in metastatic castration-resistant prostate cancer. Open questions are whether KLK2 expression persists in neuroendocrine or AR-independent disease and how it compares with PSMA as an engager target. The plain version: KLK2 is a cousin of PSA that stays stuck to cancer cells, so drugs can grab it.","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/KLK2","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/KLK2"}],"tags":["t-cell-engager-target"],"related":[],"indications":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Prevalence not recorded: no peer-reviewed KLK2 expression series with a stated denominator was found for prostate cancer; 'nearly universal' rests on KLK2 being an androgen-regulated, prostate-restricted gene rather than on a published positivity rate."],"symbol":"KLK2","hgnc":"HGNC:6363","ensembl":"ENSG00000167751","uniprot":"P20151","entrez":"3817","biology":"Serine protease activating PSA; androgen-regulated.","whereFound":["Prostate cancer (nearly universal)"],"targetClass":"surface-antigen","prevalence":[]},{"id":"mesothelin","kind":"target","name":"Mesothelin (MSLN)","aka":["MSLN"],"tldr":"A protein normally found only on the thin lining of the chest and abdomen, but made in large amounts by mesothelioma and by most pancreatic and many ovarian cancers. Because healthy organs barely make it, it is an attractive handle for antibody-based imaging and treatment.","summary":"Mesothelin is a glycosylphosphatidylinositol-anchored cell-surface glycoprotein whose normal expression is restricted to mesothelial cells lining the pleura, pericardium and peritoneum. Its physiological function is not fully established, but it binds CA-125/MUC16, an interaction implicated in the peritoneal spread of ovarian cancer, and its overexpression has been linked to activation of NF-κB, MAPK and PI3K signalling that promotes proliferation, invasion and resistance to apoptosis.\n\nMesothelin is essentially absent from normal pancreas but is expressed in close to 100% of pancreatic ductal adenocarcinomas and virtually all epithelioid (though not sarcomatoid) mesotheliomas, and in a substantial majority of ovarian carcinomas (particularly serous subtype) and roughly half of lung adenocarcinomas, giving a wide tumour-to-normal-tissue contrast that has made it a target for antibody-drug conjugates (for example DMOT4039A/anetumab), immunotoxins (SS1P, LMB-100), CAR-T therapy and radiolabelled antibodies. 89Zr-labelled anti-mesothelin antibody immunoPET (for example 89Zr-MMOT0530A) has visualised pancreatic and ovarian cancer lesions in patients, with higher mean tumour SUVmax in ovarian than pancreatic lesions, plausibly reflecting the dense desmoplastic stroma that limits antibody penetration in pancreatic tumours. A thorium-227-labelled anti-mesothelin antibody-chelator conjugate (BAY2287411) has been tested in a first-in-human alpha-therapy trial in mesothelin-expressing tumours.\n\nAs a target, mesothelin's strength is a genuinely restricted normal-tissue expression pattern combined with near-universal expression in several hard-to-treat cancers. Its main limitations are that, as an antibody target, achieving good tumour penetration in stroma-rich tumours such as pancreatic adenocarcinoma is harder than in mesothelioma or ovarian cancer, and mesothelin is also shed from the cell surface into blood and ascites, which can act as an antigen sink for circulating antibody-based agents.","asOf":"2026-09-22","links":[{"label":"PMC: mesothelin-targeted cancer immunotherapy (expression table across tumour types)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC2265108/"},{"label":"PMC: mesothelin as a biomarker for targeted therapy","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6708176/"},{"label":"Clinical Cancer Research: immunoPET with anti-mesothelin antibody (89Zr-MMOT0530A) in pancreatic and ovarian cancer","url":"https://aacrjournals.org/clincancerres/article/22/7/1642/121738/ImmunoPET-with-Anti-Mesothelin-Antibody-in"},{"label":"MDPI Cancers: mesothelin as an immunotherapeutic target, including BAY2287411 thorium-227 conjugate","url":"https://www.mdpi.com/2072-6694/14/6/1550"}],"tags":["mesothelioma","pancreatic cancer","ovarian cancer","antibody target"],"related":["zr-89","th-227"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"MSLN","biology":"A GPI-anchored cell-surface glycoprotein normally restricted to mesothelial cells lining the pleura, pericardium and peritoneum, whose interaction with CA-125/MUC16 has been implicated in the peritoneal spread of ovarian cancer. It is overexpressed in nearly all pancreatic ductal adenocarcinomas and epithelioid mesotheliomas and in most serous ovarian carcinomas, while normal organ parenchyma is negative.","whereFound":["Malignant pleural mesothelioma (epithelioid subtype): expressed in essentially all cases, absent in sarcomatoid mesothelioma","Pancreatic ductal adenocarcinoma: expressed in close to 100% of cases, absent in normal pancreas and chronic pancreatitis","Ovarian cancer (mainly serous subtype): expressed in roughly 70-100% of cases","Lung adenocarcinoma: expressed in a substantial minority of cases","Normal tissue: limited to mesothelial cells of pleura, pericardium and peritoneum"],"targetClass":"surface-antigen","prevalence":[]},{"id":"nectin4","kind":"target","name":"Nectin-4","aka":[],"tldr":"Nectin-4 is an adhesion protein plentiful on bladder cancer cells, used as the docking site for the ADC enfortumab vedotin.","summary":"Nectin-4 is expressed at high levels in urothelial carcinoma and also in breast, lung, and pancreatic cancers. Enfortumab vedotin plus pembrolizumab is first-line standard in advanced urothelial cancer (EV-302). Next-generation Nectin-4 ADCs with topoisomerase-I payloads (MK-3120) and Nectin-4×TROP2 bispecific ADCs (AK146D1, AVZO-103) are in development.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Nectin-4","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Nectin-4"}],"tags":["adc-target"],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"NECTIN4","hgnc":"HGNC:19688","ensembl":"ENSG00000143217","uniprot":"Q96NY8","entrez":"81607","biology":"Nectin-4 is a cell adhesion molecule and also a receptor for measles virus. Skin expression explains the rash seen with enfortumab.","whereFound":["Urothelial carcinoma (>80%)","TNBC","NSCLC","Pancreatic"],"targetClass":"surface-antigen","prevalence":[]},{"id":"nis-symporter","kind":"target","name":"NIS (sodium-iodide symporter)","aka":["Sodium/iodide cotransporter","SLC5A5"],"tldr":"A protein in the thyroid that pulls iodine out of the blood to make thyroid hormone. It is the reason radioactive iodine can find and treat thyroid cancer almost anywhere in the body.","summary":"NIS is a 13-transmembrane-domain glycoprotein on the basolateral membrane of thyroid follicular cells that actively co-transports two sodium ions with one iodide ion, using the electrochemical sodium gradient generated by Na+/K+-ATPase, as the first step of thyroid hormone synthesis. Its expression in the thyroid is driven by thyroid-stimulating hormone (TSH) acting through the cAMP pathway, which is why thyroid-stimulating hormone withdrawal or recombinant human TSH (thyrotropin alfa) is used clinically to maximise iodide uptake before radioiodine scanning or therapy.\n\nMore than 70% of differentiated (papillary and follicular) thyroid cancers retain enough NIS expression to concentrate iodide, which is the biological basis of whole-body radioiodine scanning and I-131 therapy for remnant ablation and metastatic disease. NIS is also expressed, at lower levels, in several extrathyroidal tissues: salivary glands, gastric mucosa, lactating breast, lacrimal glands, choroid plexus and placenta. Uptake in salivary glands and stomach is well below thyroid levels and the absorbed dose in these tissues is small relative to the thyroid, but it is still the mechanism behind the sialadenitis (dry mouth, taste change) and, less often, gastritis seen after high-activity I-131 therapy.\n\nAs a target, NIS is close to ideal for differentiated thyroid cancer: high density, non-internalising simple ion transport, and near-total tissue restriction outside a few low-uptake sites. Its main practical limitation is that a minority of thyroid cancers dedifferentiate and lose NIS expression (radioiodine-refractory disease), and normal-tissue uptake in salivary gland and stomach still causes most of the non-thyroid toxicity of I-131 therapy.","asOf":"2026-09-22","links":[{"label":"PMC: modulation of NIS expression in salivary gland tissue and I-131 uptake","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC3752512/"},{"label":"PMC: the sodium iodide symporter (NIS) - regulation and approaches to therapy","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC3408573/"},{"label":"PMC: sodium/iodide symporter - molecular physiology and preclinical applications (tissue distribution table)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5739519/"},{"label":"MedlinePlus Genetics: SLC5A5 gene","url":"https://medlineplus.gov/genetics/gene/slc5a5/"}],"tags":["thyroid","ion transporter","theranostics"],"related":["radioactive-iodine","radioiodine-therapy","thyroid","thyrotropin-alfa","radioiodine-term","i-131"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"SLC5A5","biology":"A basolateral membrane glycoprotein that actively co-transports two sodium ions with one iodide ion into thyroid follicular cells, the first step of thyroid hormone synthesis, driven by TSH via the cAMP pathway. Because most differentiated thyroid cancer retains this transporter, it is the biological basis for diagnostic and therapeutic use of radioactive iodine.","whereFound":["Thyroid follicular cells: high, TSH-driven expression; basis of normal thyroid hormone synthesis","Differentiated thyroid cancer: retained in >70% of papillary and follicular carcinomas","Salivary gland striated ducts: moderate expression, clinically relevant because of I-131 sialadenitis","Gastric mucosa (basolateral): moderate expression, secretes iodide into gastric juice","Lactating mammary gland, lacrimal gland, choroid plexus, placenta: lower-level physiological expression"],"targetClass":"other","prevalence":[]},{"id":"norepinephrine-transporter","kind":"target","name":"Norepinephrine transporter (NET)","aka":["NET","Noradrenaline transporter"],"tldr":"A protein on nerve cells and adrenal-type tumour cells that pulls noradrenaline back inside after it has been released. A radioactive drug called MIBG looks and acts enough like noradrenaline that this same protein carries it into neuroblastoma and phaeochromocytoma cells, so doctors can see or treat the tumour.","summary":"The norepinephrine transporter is a 12-transmembrane-domain protein of presynaptic sympathetic neurons and adrenal medullary chromaffin cells that terminates noradrenergic signalling by taking norepinephrine back into the cell (uptake-1), an active, sodium- and chloride-dependent, ATP-driven process roughly 50-fold more efficient than passive diffusion. Once inside, norepinephrine (and NET's synthetic analogue metaiodobenzylguanidine, MIBG) can be stored in secretory vesicles via the vesicular monoamine transporters (VMAT1/2) or remain in the cytoplasm.\n\nTumours that arise from sympathetic neural crest precursors - neuroblastoma, phaeochromocytoma and paraganglioma - retain NET expression at high frequency (around 90% of neuroblastomas are NET-positive), and expression correlates with MIBG avidity on imaging. Radioiodinated MIBG (123I for diagnosis, 131I for therapy) is taken up through NET, giving both a diagnostic scan and, at therapeutic activities, a targeted radiotherapy. Other transporters (OCT1-3, MATE1/2-K) contribute to non-specific uptake into liver, salivary gland and heart and to renal clearance, and drugs that block NET (tricyclic antidepressants, some stimulants) must be stopped before MIBG scanning or therapy because they blunt tumour uptake.\n\nAs a target, NET's strength is high, tumour-restricted expression in an otherwise hard-to-image tumour family, plus intracellular retention via VMAT once inside the cell. Its main limitations are heterogeneous expression (MYCN-amplified, poorly differentiated neuroblastomas tend to have lower NET expression and are less MIBG-avid) and competition from other transporters that reduce specificity and complicate dosimetry.","asOf":"2026-09-22","links":[{"label":"DMD: clinical applications and roles of transporters in disposition, tumour targeting and tissue toxicity of MIBG","url":"https://dmd.aspetjournals.org/content/50/9/1218"},{"label":"JNM (SNMMI supplement): norepinephrine transporter as a target for imaging and therapy","url":"https://jnm.snmjournals.org/content/58/Supplement_2/39S"},{"label":"PMC: 'Nothing but NET' - NET expression and efficacy of 131I-MIBG therapy","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4237663/"}],"tags":["neuroendocrine","paediatric","transporter"],"related":["i131-mibg","iobenguane-i-131","mibg-theranostics","pheochromocytoma-paraganglioma","neuroblastoma","neuroblastoma-high-risk","metastatic-ppgl","hereditary-ppgl","idea-mfbg-pet-replaces-mibg","nct04724369","paper-pryma-high-specific-activity-i131-mibg-ppgl-jnm-2019","i-123","i-131"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"SLC6A2","biology":"A presynaptic membrane transporter that takes norepinephrine back into sympathetic neurons and adrenal chromaffin cells after release, an active sodium- and chloride-dependent process. Tumours arising from sympathetic neural crest precursors (neuroblastoma, phaeochromocytoma, paraganglioma) retain this transporter at high frequency, allowing the norepinephrine analogue MIBG to be carried into tumour cells for imaging and therapy.","whereFound":["Neuroblastoma: NET-positive in roughly 90% of tumours; MYCN-amplified tumours tend to have lower expression","Phaeochromocytoma and paraganglioma: NET expressed in chromaffin-derived tumour cells, uptake reinforced by VMAT storage","Normal sympathetic nerve terminals and adrenal medulla: physiological expression"],"targetClass":"other","prevalence":[]},{"id":"parp","kind":"target","name":"PARP","aka":["PARP1/2","Poly [ADP-ribose] polymerase 2"],"tldr":"PARP is a DNA repair enzyme. Cancers that have already lost one repair system (BRCA) die when this second one is blocked; healthy cells survive.","summary":"PARP inhibitors (olaparib, niraparib, rucaparib, talazoparib) exploit synthetic lethality with BRCA1/2 mutations and homologous recombination deficiency in ovarian, breast, prostate, and pancreatic cancer. Olaparib is approved in adjuvant germline-BRCA breast cancer (OlympiA). PARP1-selective inhibitors (saruparib) and PARP PET tracers are the next step.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/PARP_inhibitor","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/PARP_inhibitor"}],"tags":["synthetic-lethality"],"related":[],"indications":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"PARP1","hgnc":"HGNC:270","ensembl":"ENSG00000143799","uniprot":"P09874","entrez":"142","biology":"Poly(ADP-ribose) polymerase 1 senses single-strand breaks; trapping on DNA is the key cytotoxic mechanism.","whereFound":["BRCA/HRD ovarian, breast, prostate, pancreatic cancers"],"targetClass":"enzyme","prevalence":[{"indicationId":"prostate","pct":"20-25","measure":"HRR gene alteration (mCRPC)","source":"https://www.cbioportal.org/study/summary?id=prad_tcga_pan_can_atlas_2018","note":"BRCA2 ~8-10%"}]},{"id":"psma","kind":"target","name":"PSMA","aka":[],"tldr":"A protein on prostate cancer cells that lets doctors both see the cancer on a PET scan and hit it with a radioactive drug.","summary":"Prostate-specific membrane antigen is the archetypal theranostic target. PSMA PET (Pylarify, Illuccix, Locametz, Pylarify TruVu) is standard for staging; 177Lu-PSMA-617 (Pluvicto) is approved before and after chemotherapy in metastatic castration-resistant prostate cancer. Alpha-emitting 225Ac-PSMA agents and PSMA-targeted bispecifics and CAR-T are in trials.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Glutamate_carboxypeptidase_II","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Glutamate_carboxypeptidase_II"}],"tags":["theranostic","pet-target"],"related":["lu-177","ac-225"],"indications":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":["aaa817","jnj-87189401","hrs-4357","fpi-2265"],"companies":["artbio","convergent-therapeutics","point-biopharma"],"institutions":[],"pathways":["prostate-cancer-signalling"],"terms":[],"trials":["nct07567521","nct06383052","nct05381103","nct06906471","nct07258407"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"FOLH1","hgnc":"HGNC:3788","ensembl":"ENSG00000086205","uniprot":"Q04609","entrez":"2346","biology":"PSMA is a type II transmembrane glutamate carboxypeptidase; expression increases with grade and castration resistance. Also expressed in tumour neovasculature of other cancers.","whereFound":["Prostate cancer (>90%)","Neovasculature of RCC, glioma, others"],"targetClass":"surface-antigen","prevalence":[{"indicationId":"prostate","pct":">90","measure":"PSMA PET positivity, metastatic disease","source":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12796145/","note":"~10% PSMA-negative or low"},{"indicationId":"rcc","pct":"60-80","measure":"Neovascular PSMA expression","source":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12796145/","note":"Clear-cell; imaging studies"}]},{"id":"sstr2","kind":"target","name":"Somatostatin receptor 2","aka":[],"tldr":"Somatostatin receptor 2 is a hormone receptor densely present on neuroendocrine tumours, and was the first theranostic target to reach routine care.","summary":"Somatostatin receptor 2 is a G-protein-coupled receptor overexpressed on well-differentiated neuroendocrine tumours, which internalise bound somatostatin analogues and so can be both imaged and treated with the same peptide. 68Ga-DOTATATE PET (Netspot) and 177Lu-DOTATATE (Lutathera, NETTER-1 and NETTER-2) established the theranostic paradigm, in which a diagnostic scan selects patients for a matched radioligand. SSTR PET is positive in 80-90% of well-differentiated neuroendocrine tumours but lower in grade 3, and the receptor is also expressed in meningioma, 30-50% of small-cell lung cancer, and some breast cancers. Alpha-emitting 225Ac-DOTATATE (RYZ101) and 212Pb-DOTAMTATE are in phase 3, testing whether alpha particles outperform beta. The simple version is a hormone receptor that lets doctors see and treat neuroendocrine tumours with the same molecule.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Somatostatin_receptor_2","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Somatostatin_receptor_2"}],"tags":["theranostic"],"related":["ga-68","lu-177","ac-225","pb-212"],"indications":["neuroendocrine","sclc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":["point-biopharma"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"SSTR2","hgnc":"HGNC:11331","ensembl":"ENSG00000180616","uniprot":"P30874","entrez":"6752","biology":"G-protein-coupled receptor; also expressed in meningioma, small-cell lung cancer, and some breast cancers.","whereFound":["Neuroendocrine tumours","Meningioma","Small-cell lung cancer (subset)"],"targetClass":"surface-antigen","prevalence":[{"indicationId":"neuroendocrine","pct":"80-90","measure":"SSTR PET positivity (well-differentiated)","source":"https://en.wikipedia.org/wiki/Somatostatin_receptor_2","note":"Lower in grade 3"},{"indicationId":"sclc","pct":"30-50","measure":"IHC/imaging","source":"https://en.wikipedia.org/wiki/Somatostatin_receptor_2"}]},{"id":"sortilin","kind":"target","name":"Sortilin (SORT1)","aka":["SORT1","Neurotensin receptor 3","NTSR3","Gp95"],"tldr":"A receptor that pulls molecules into cells and is found at high levels in several cancers, including ovarian, endometrial and triple-negative breast cancer. A peptide-drug conjugate against it is in a phase 1 trial, and the first radioactive pair (one version for scans, one for treatment) was published in 2026.","summary":"Sortilin, encoded by SORT1 (HGNC:11186), is a sorting receptor that carries bound ligands such as neurotensin and progranulin into cells. That internalising function is what drug developers exploit. Theratechnologies built TH19P01, a peptide that needs sortilin to enter cells, and conjugated it to docetaxel as TH1902 (sudocetaxel zendusortide). In their preclinical work, high sortilin expression correlated with shorter survival in triple-negative breast cancer, more than 75% of clinically annotated ovarian and endometrial tumours showed high sortilin by immunohistochemistry, and TH1902 outperformed unconjugated docetaxel in xenografts without causing neutropenia. The phase 1 trial in advanced solid tumours, NCT04706962, started in March 2021 and is listed as active, not recruiting.\n\nThe radiopharmaceutical side is new. In March 2026 a Peking University group labelled the anti-sortilin antibody latozinemab to make [89Zr]Zr-DFO-latozinemab for PET and [177Lu]Lu-DOTA-latozinemab for therapy. Melanoma tissue showed high sortilin (mean H-score 189.79); the PET agent gave high-contrast tumour images peaking at 72 hours; the lutetium conjugate reached 39.08% injected dose per gram in tumour at 72 hours; and 11.1 MBq significantly slowed tumour growth. The authors describe it as the first sortilin-directed theranostic pair.\n\nWhat is missing is anything between a full antibody with multi-day kinetics and the peptide carrying a chemotherapy payload: no small-molecule or peptide sortilin radioligand, and no human imaging data, has been published.","asOf":"2026-09-24","links":[{"label":"HGNC: SORT1 gene record (HGNC:11186)","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:11186"},{"label":"Gao et al., J Med Chem 2026: 89Zr/177Lu radioimmunoconjugates targeting SORT1 (PMID 41773941)","url":"https://pubmed.ncbi.nlm.nih.gov/41773941/"},{"label":"Currie et al., Cancers 2022: TH1902 against sortilin-positive ovarian and endometrial cancers (PMID 35454785)","url":"https://pubmed.ncbi.nlm.nih.gov/35454785/"},{"label":"Demeule et al., Cancer Sci 2021: TH1902 for sortilin-positive triple-negative breast cancer (PMID 34314556)","url":"https://pubmed.ncbi.nlm.nih.gov/34314556/"},{"label":"ClinicalTrials.gov NCT04706962: TH1902 in patients with advanced solid tumours","url":"https://clinicaltrials.gov/study/NCT04706962"}],"tags":["internalising receptor","peptide-drug conjugate","theranostic pair"],"related":["peptide-drug-conjugate","zr-89","lu-177","immuno-pet","radioimmunotherapy","breast-triple-negative"],"indications":["breast-triple-negative"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"SORT1","biology":"A type I membrane sorting receptor of the VPS10P family that binds neurotensin, progranulin and other ligands and carries them into the cell, which makes it an internalising gateway for conjugated drugs or radionuclides.","whereFound":["Ovarian and endometrial cancer: high expression in more than 75% of clinically annotated tumours (Theratechnologies immunohistochemistry series)","Triple-negative breast cancer: high expression associated with shorter survival, particularly with nodal metastases","Melanoma: high expression on tissue microarray (mean H-score 189.79) and upregulated in transcriptional data across several cancers","Normal brain and other tissues, where it traffics neurotrophins and lysosomal cargo"],"targetClass":"surface-antigen","prevalence":[]},{"id":"steap1","kind":"target","name":"STEAP1","aka":[],"tldr":"STEAP1 is a protein on the surface of most prostate cancer cells, now the address for a T-cell engager in phase 3.","summary":"Six-transmembrane epithelial antigen of the prostate 1 is expressed in most prostate cancers including PSMA-low and neuroendocrine-like disease, with limited normal expression. Xaluritamig (STEAP1×CD3 XmAb 2+1) produced PSA50 in ~half of heavily pretreated mCRPC patients at target doses in phase 1 and is in two phase 3 trials (XALute post-taxane; XALience with abiraterone chemo-naive). Also an ADC target historically (vandortuzumab vedotin, discontinued).","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/STEAP1","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/STEAP1"}],"tags":["t-cell-engager-target"],"related":[],"indications":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Prevalence not recorded: no peer-reviewed STEAP1 expression series with a stated denominator was found for prostate cancer; the widely repeated '>80%' figure could not be traced to a series with an n, so it has been removed."],"symbol":"STEAP1","hgnc":"HGNC:11378","ensembl":"ENSG00000164647","uniprot":"Q9UHE8","entrez":"26872","biology":"STEAP1 is a metalloreductase at cell junctions, upregulated by androgen receptor signalling; its expression is partly independent of PSMA, making it complementary.","whereFound":["Prostate cancer (most cases)","Ewing sarcoma","Bladder (subset)"],"targetClass":"surface-antigen","prevalence":[]},{"id":"tau-protein","kind":"target","name":"Tau protein (neurofibrillary tangles)","aka":["PHF-tau","aggregated tau","NFTs"],"tldr":"A protein that normally helps hold nerve cells together but, in Alzheimer's disease, twists into tangles inside the cells. A PET tracer called flortaucipir binds these tangles so doctors can see how far the disease has spread in the brain.","summary":"Tau is a microtubule-associated protein that, in Alzheimer's disease, becomes abnormally hyperphosphorylated and aggregates intracellularly into paired helical filaments that form neurofibrillary tangles (NFTs) - one of the two pathologies (with amyloid beta plaques) required for a neuropathological diagnosis of Alzheimer's disease. Tangles accumulate and spread through the brain in a stereotyped anatomical sequence (Braak staging), which is why tau PET, unlike amyloid PET, can track disease stage and distribution rather than simple positive/negative status.\n\nFlortaucipir F18 (Tauvid) binds aggregated PHF-tau with a dissociation constant of 0.57 nM in vitro and shows negligible binding to beta-amyloid, so it reports tangle pathology specifically. It was FDA-approved in May 2020, the first and to date only approved tau PET tracer, for estimating the density and distribution of NFTs in adults with cognitive impairment being evaluated for Alzheimer's disease; it is explicitly not indicated for chronic traumatic encephalopathy, because non-Alzheimer's tauopathies show different tau conformations that the tracer does not reliably detect. Some off-target binding to monoamine oxidase A/B occurs, seen in the choroid plexus, striatum and brainstem, and is excluded from image interpretation.\n\nAs a target, tau's strength is that its regional distribution tracks clinical stage and correlates better with cognitive decline than amyloid burden does. Its main limitation is that flortaucipir's sensitivity is lower in earlier-stage disease (the pivotal studies enrolled mostly terminally ill patients with advanced NFT pathology), and it cannot distinguish Alzheimer's tau from other tauopathies.","asOf":"2026-09-22","links":[{"label":"FDA label: Tauvid (flortaucipir F 18 injection)","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/212123s031lbl.pdf"},{"label":"FDA integrated review, NDA 212123 (mechanism of action, pivotal trial data)","url":"https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212123Orig1s000IntegratedR.pdf"},{"label":"PMC: Tauvid, the first FDA-approved PET tracer for imaging tau pathology in Alzheimer's disease","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7911942/"},{"label":"Eli Lilly: FDA approval of Tauvid (28 May 2020)","url":"https://investor.lilly.com/node/43256/pdf"}],"tags":["neurology","Alzheimer's disease","protein aggregate"],"related":["amyloid-beta","f-18"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"biology":"A microtubule-associated protein that becomes hyperphosphorylated and aggregates intracellularly into paired helical filaments forming neurofibrillary tangles, the second defining pathology of Alzheimer's disease. Tangles spread through the brain in a stereotyped anatomical sequence that correlates with clinical stage, distinguishing tau imaging from the simple positive/negative readout of amyloid imaging.","whereFound":["Alzheimer's disease: neurofibrillary tangles accumulate in a stereotyped pattern (Braak staging), correlating with cognitive impairment stage","Other tauopathies (progressive supranuclear palsy, Pick's disease, chronic traumatic encephalopathy): different tau conformations, not reliably detected by flortaucipir"],"targetClass":"other","prevalence":[]},{"id":"trop2","kind":"target","name":"TROP2","aka":[],"tldr":"TROP2 is a surface glycoprotein present at high levels on most epithelial cancers (breast, lung, urothelial, gastric, pancreatic) and at low levels on normal tissue. It does not drive the cancer; it is a delivery address, used by the approved ADCs sacituzumab govitecan and datopotamab deruxtecan and by sacituzumab tirumotecan, with a TROP2 PET tracer in development to pick patients.","summary":"Trophoblast cell-surface antigen 2 is a transmembrane glycoprotein overexpressed in most epithelial cancers (breast, lung, urothelial, gastric, pancreatic) with low normal-tissue expression. It is not an oncogenic driver; it is a delivery address. Three TROP2 ADCs are approved or in registration (sacituzumab govitecan, datopotamab deruxtecan, sacituzumab tirumotecan) and a TROP2 PET tracer is in development to select patients.","asOf":"2026-09-04","links":[{"label":"UniProt P09758: TACSTD2 (TROP2)","url":"https://www.uniprot.org/uniprotkb/P09758/entry"}],"tags":["adc-target","pet-target"],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"TACSTD2","hgnc":"HGNC:11530","ensembl":"ENSG00000184292","uniprot":"P09758","entrez":"4070","biology":"Regulates calcium signalling and cell adhesion; overexpression correlates with poor prognosis. Expression is heterogeneous within tumours, which limits the value of IHC selection. Internalises on antibody binding and traffics to lysosomes, which is what makes it a good ADC target.","whereFound":["Triple-negative breast cancer (~80-90% express)","HR+ breast cancer","NSCLC","Urothelial carcinoma","Gastric, pancreatic, endometrial cancers"],"targetClass":"surface-antigen","prevalence":[]},{"id":"upar","kind":"target","name":"uPAR (urokinase plasminogen activator receptor)","aka":["uPAR","PLAUR"],"tldr":"A protein that helps cancer cells break through surrounding tissue and spread. Higher amounts on a tumour are linked to more aggressive disease, and a PET tracer built on a small peptide can measure how much of it a tumour has.","summary":"uPAR is a glycosylphosphatidylinositol-anchored cell-surface receptor for urokinase-type plasminogen activator (uPA); the uPA/uPAR system focuses proteolytic activity (activation of plasmin, which degrades extracellular matrix) at the cell surface, driving tumour cell invasion, matrix remodelling and metastasis. uPAR overexpression is an established biomarker of tumour aggressiveness across several common cancers, including prostate, breast, bladder and glioma, and correlates with independent prognostic information beyond PSA and Gleason score in prostate cancer.\n\nThe PET ligand 68Ga-NOTA-AE105 (and the earlier 64Cu-DOTA-AE105), based on the high-affinity peptide antagonist AE105, has been evaluated in first-in-human and phase 2 studies in prostate cancer, breast cancer, bladder cancer and glioma. In localised prostate cancer, tumour SUVmax on 68Ga-NOTA-AE105 PET correlated significantly with Gleason score (Spearman ρ = 0.55), and a SUVmax cut-off achieved 96% sensitivity for detecting Gleason score ≥3+4, raising the possibility of uPAR PET reducing the number of repeat biopsies needed in active surveillance. In glioma, uPAR-PET uptake was associated with worse overall and progression-free survival.\n\nAs a target, uPAR's strength is a genuine link to tumour aggressiveness and metastatic potential across multiple tumour types, giving it prognostic as well as localising value. Its main limitation to date is that all published clinical PET data come from small studies run predominantly by one research group, so multicentre validation is still needed, and no uPAR-targeted therapeutic radioligand has reached clinical use.","asOf":"2026-09-22","links":[{"label":"JNM: uPAR PET/MRI (68Ga-NOTA-AE105) and Gleason score correlation in prostate cancer","url":"https://jnm.snmjournals.org/content/62/3/354"},{"label":"PMC: PET imaging of uPAR in prostate cancer (review)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5118403/"},{"label":"JNM: first-in-human study of 68Ga-NOTA-AE105 for uPAR PET imaging","url":"https://jnm.snmjournals.org/content/58/3/379"},{"label":"EJNMMI Research: phase 2 trial of 68Ga-NOTA-AE105 uPAR PET in glioma, survival correlation","url":"https://ejnmmires.springeropen.com/articles/10.1186/s13550-024-01164-9"}],"tags":["invasion","prostate cancer","prognostic biomarker"],"related":["prostate","nct06474806","ga-68","cu-64"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"PLAUR","biology":"A GPI-anchored cell-surface receptor for urokinase-type plasminogen activator that focuses proteolytic activity at the cell surface, activating plasmin to degrade extracellular matrix and drive tumour invasion and metastasis. Its overexpression is an established biomarker of tumour aggressiveness in prostate, breast, bladder cancer and glioma.","whereFound":["Prostate cancer: uPAR expression correlates with Gleason score and aggressiveness","Glioma: uPAR-PET uptake associated with tumour grade and worse survival","Breast cancer and urinary bladder cancer: uPAR overexpression linked to invasive and metastatic potential","Normal tissue: low background expression, contributing to good image contrast"],"targetClass":"surface-antigen","prevalence":[]}]