{"entity":{"id":"opp-cldn18-2-imaging-gastric","kind":"opportunity","name":"Claudin-18.2 imaging when one biopsy says negative","aka":["CLDN18.2 PET","claudin 18.2 imaging"],"tldr":"Stomach cancer patients now get a drug only if a biopsy shows a protein called claudin-18.2. One biopsy core finds it only about six times in ten when the whole tumour has it, so patients are being refused a treatment on a test that misses.","summary":"Zolbetuximab is approved in the US, EU, Japan, China and elsewhere for CLDN18.2-positive, HER2-negative gastric and gastro-oesophageal junction adenocarcinoma, with patient selection by the VENTANA CLDN18 (43-14A) RxDx immunohistochemistry assay. Roughly 38% of screened patients in the pooled SPOTLIGHT and GLOW populations were positive at the 75%-of-tumour-cells threshold. In June 2026 China's regulator approved satricabtagene autoleucel, a CLDN18.2 CAR-T, in the same biomarker-defined population, so the number of decisions resting on this one assay is rising.\n\nThe assay's weakness is measurable. Against whole-tumour-section ground truth, a single representative biopsy gave 58.8% sensitivity for CLDN18.2, rising to 76.5% with six to eight biopsies, and a minimum of six endoscopic biopsies was needed to keep false negatives down; 18% of tumours were discordant between the primary and the matched nodal metastasis. A multi-laboratory ring trial found a 12% false-negative rate with 91% overall accuracy.\n\nThe imaging work is almost entirely Chinese and early: 68Ga-PMD22, 68Ga-NC-BCH and 124I-18B10(10L) each have a published pilot of 11 to 17 patients, and none has entered a multicentre or registration trial. The opportunity is therefore unusually well specified for a crossover case, because the incumbent test's failure rate is published and the decision it gates is binary.","asOf":"2026-09-23","links":[{"label":"Single-biopsy sensitivity for CLDN18.2, Scientific Reports 2025","url":"https://www.nature.com/articles/s41598-025-12337-4"},{"label":"CLDN18.2 positivity in pooled SPOTLIGHT and GLOW screening","url":"https://link.springer.com/article/10.1007/s10120-024-01518-1"},{"label":"First-in-human CLDN18.2 PET imaging","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11149600/"},{"label":"Multi-laboratory ring trial of CLDN18.2 immunohistochemistry","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12647276/"},{"label":"Gastric cancer biomarker testing review, naming the approved assay","url":"https://www.cancerbiomed.org/content/22/3/212"}],"tags":["target crossover","gastric","companion diagnostic","sampling error"],"related":["ga-68","i-124"],"indications":["gastric-oesophageal-cancer"],"sections":[],"technologies":["immuno-pet","pet-ct"],"targets":["cldn18-2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"lens":"target-crossover","unmetNeed":"When a gastric cancer biopsy reads CLDN18.2-negative, no test distinguishes a truly negative tumour from a false negative caused by sampling, so patients may be denied an approved antibody or CAR-T on a result that a single core gets right only about six times in ten.","useCase":"A gastrointestinal oncologist would order the scan for the patient whose biopsy is CLDN18.2-negative or equivocal but whose clinical situation makes the drug worth having, and for the patient whose only accessible tissue is an old primary specimen while the disease now sits in nodes and peritoneum. A positive scan would justify re-biopsy or treatment; a negative scan across all disease would close the question.","hypothesis":"Whole-body CLDN18.2 imaging will identify patients whose single-biopsy immunohistochemistry is falsely negative, at a rate consistent with the published 12% laboratory false-negative rate and the 41% single-core miss rate, and will thereby qualify patients for approved CLDN18.2-directed therapy who are currently refused it.","rationale":"Three independent Chinese groups have shown that CLDN18.2 can be imaged in patients, and the target is a tight-junction protein whose accessibility in tumour tissue is what makes the therapeutic antibody work. The incumbent test's failure mode is documented with numbers, from both a whole-section comparison and a ring trial, and 18% primary-versus-node discordance is exactly the kind of error whole-body imaging addresses. Two approved therapies now depend on this selection step, one of them a CAR-T, which raises the cost of a false negative.","test":"A prospective study in patients with gastric or junctional adenocarcinoma enrolling on the basis of a CLDN18.2-negative or equivocal biopsy, imaging all patients and then taking a protocol-mandated multi-core re-biopsy of a scan-positive lesion, with the primary endpoint being the proportion of scan-positive patients whose re-biopsy is positive at the label threshold. That design directly measures the false-negative rescue rate the case rests on.","maturity":"early-clinical","verdict":"companion-only","mostAdvanced":"Three Chinese first-in-human PET tracers (68Ga-PMD22, 68Ga-NC-BCH, 124I-18B10(10L)) with published pilots of 11 to 17 patients; none in a multicentre or registration trial.","dueDiligence":[{"domain":"target-biology","state":"strong","why":"CLDN18.2 positivity at the 75% threshold was 38.4% across 4,507 patients screened for SPOTLIGHT and GLOW, and Astellas reports approximately 35% positivity in Chinese patients with advanced disease.","source":"Pooled screening analysis, Gastric Cancer 2024","url":"https://link.springer.com/article/10.1007/s10120-024-01518-1","weighted":true},{"domain":"clinical-evidence","state":"thin","why":"Three separate first-in-human tracer studies of 11 to 17 patients each, all single-centre and all in China; no comparative or multicentre data.","source":"Published pilot studies","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11149600/"},{"domain":"diagnostic-performance","state":"moderate","why":"The case is built on the incumbent's measured failure: 58.8% sensitivity from one representative biopsy against whole-section truth, 76.5% with six to eight biopsies, 18% primary-versus-node discordance, and a 12% false-negative rate in a multi-laboratory ring trial.","source":"Naujoks et al., Scientific Reports 2025; ring trial","url":"https://www.nature.com/articles/s41598-025-12337-4","weighted":true},{"domain":"safety-dosimetry","state":"thin","why":"No adverse events reported in the small published cohorts; the iodine-124 construct carries a higher radiation burden than the gallium-68 ones, and no formal comparison has been published."},{"domain":"regulatory-path","state":"moderate","why":"An approved companion diagnostic already defines the claim: the VENTANA CLDN18 (43-14A) RxDx assay. An imaging agent would have to be positioned against it, most plausibly as an adjunct where tissue is inadequate rather than as a replacement.","source":"Gastric cancer biomarker review","url":"https://www.cancerbiomed.org/content/22/3/212"}],"flags":[{"category":"technical","flag":"amber","why":"Gastric wall and gastro-oesophageal junction imaging sits next to physiological uptake, and the published agents are antibody or antibody-fragment based with the kinetics that implies."},{"category":"unmet-need","flag":"green","why":"A binary treatment decision gated by a test with a published 12% laboratory false-negative rate and a 41% single-core miss rate against whole-section truth."},{"category":"ip","flag":"amber","why":"The binders come from therapeutic antibody programmes and the published imaging work sits with Chinese academic centres and their partners."},{"category":"commercial","flag":"amber","why":"Companion-only by construction, but tied to two approved therapies in a disease with an estimated 980,000 new cases a year, and the CAR-T approval raises the cost of a false negative."},{"category":"isotope","flag":"green","why":"Gallium-68 works for two of the three published agents; the iodine-124 version would be harder to distribute."},{"category":"competition","flag":"amber","why":"Three groups are already in humans, all in China, so a Western programme would be following rather than leading the science."}],"competition":[{"name":"Chinese academic PET programmes","what":"68Ga-PMD22, 68Ga-NC-BCH and 124I-18B10(10L), each with a published first-in-human pilot of 11 to 17 patients.","stage":"first-in-human","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11149600/"},{"name":"Astellas","what":"Zolbetuximab (Vyloy), the approved CLDN18.2 antibody, selected by the VENTANA 43-14A RxDx immunohistochemistry companion diagnostic.","stage":"approved","url":"https://www.prnewswire.com/news-releases/chinas-national-medical-products-administration-nmpa-approves-vyloy-zolbetuximab-for-first-line-treatment-of-advanced-gastric-or-gastroesophageal-junction-adenocarcinoma-302342446.html"},{"name":"CARsgen Therapeutics","what":"Satricabtagene autoleucel, a CLDN18.2 CAR-T reported approved in China in June 2026 for the same biomarker-defined population.","stage":"approved in China","url":"https://chinamedwaypoint.com/resources/cancer-care/cancer-care-in-china/car-t-cell-therapy/ct041-satri-cel-cldn18-2-gastric-cancer-nmpa-approval"},{"name":"Roche Diagnostics","what":"The VENTANA CLDN18 (43-14A) RxDx assay, the incumbent companion diagnostic an imaging agent would be measured against.","stage":"approved companion diagnostic","url":"https://www.cancerbiomed.org/content/22/3/212"}],"differentiation":"The competitor is an approved immunohistochemistry companion diagnostic, not a blood test: liquid biopsy is not used clinically to determine CLDN18.2 status. Imaging does not offer a better biological measurement than histology; it offers coverage of every lesion at once, which is precisely the axis on which the tissue assay has been shown to fail.","metrics":[{"label":"Sensitivity of one representative biopsy for CLDN18.2 against whole-section truth","value":"58.8%","source":"Naujoks et al., Scientific Reports 2025","url":"https://www.nature.com/articles/s41598-025-12337-4"},{"label":"False-negative rate across laboratories in a CLDN18.2 immunohistochemistry ring trial","value":"12%","source":"Multi-laboratory ring trial","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12647276/"},{"label":"CLDN18.2 positivity at the 75% threshold in 4,507 screened patients","value":"38.4%","source":"Pooled SPOTLIGHT and GLOW screening, Gastric Cancer 2024","url":"https://link.springer.com/article/10.1007/s10120-024-01518-1"},{"label":"Tumours discordant between primary and matched nodal metastasis","value":"18%","source":"Naujoks et al., Scientific Reports 2025","url":"https://www.nature.com/articles/s41598-025-12337-4"}],"risks":["Regulators may not accept an imaging agent as an alternative route to a therapy whose label names a specific tissue assay, leaving the scan as an adjunct that nobody reimburses.","A scan threshold equivalent to the 75%-of-cells histology cut-off has not been defined, and defining it is a study in itself.","Three Chinese groups are ahead in the clinic, so a later entrant needs a better construct, not just a programme."],"watch":["Whether any of the three published tracers moves to a multicentre trial or reports agreement against the approved companion diagnostic.","Label expansions of CLDN18.2 therapies into earlier lines, which would multiply the number of selection decisions.","Any regulatory statement on non-tissue routes to establishing CLDN18.2 positivity."]},"route":"/opportunities/opp-cldn18-2-imaging-gastric/","neighbours":{"isotope":[{"id":"ga-68","kind":"isotope","name":"Gallium-68","route":"/isotopes/ga-68/"},{"id":"i-124","kind":"isotope","name":"Iodine-124","route":"/isotopes/i-124/"}],"indication":[{"id":"gastric-oesophageal-cancer","kind":"indication","name":"Gastric and gastro-oesophageal junction adenocarcinoma","route":"/indications/gastric-oesophageal-cancer/"}],"technology":[{"id":"immuno-pet","kind":"technology","name":"Immuno-PET","route":"/technologies/immuno-pet/"},{"id":"pet-ct","kind":"technology","name":"PET/CT","route":"/technologies/pet-ct/"}],"target":[{"id":"cldn18-2","kind":"target","name":"Claudin-18.2","route":"/targets/cldn18-2/"}]}}