{"entity":{"id":"pb-212-psv359","kind":"drug","name":"Lead-212 PSV359","aka":["[212Pb]PSV359","PSV359","PSV377 (imaging analogue)"],"tldr":"A drug that homes to the scaffolding cells tumours build around themselves, carrying a radioactive metal that fires alpha particles over a very short range. A matching scan version shows first whether a patient's tumour has the target.","summary":"PSV359 is Perspective Therapeutics' lead-212 radioligand against fibroblast activation protein alpha, the marker of cancer-associated fibroblasts. FAP-alpha is attractive because it is present in the stroma of most epithelial cancers and nearly absent from normal adult tissue, and because high expression tracks with poor prognosis in non-small cell lung, colorectal, pancreatic, gastric, mesothelioma, head and neck, oesophageal and ovarian cancers.\n\nThe first-in-human phase 1/2 study, NCT06710756, opened in April 2025 with a planned 112 participants and uses the pair directly: [203Pb]PSV359 to image and [212Pb]PSV359 to treat. Its original tumour list was pancreatic, gastric and gastro-oesophageal junction, oesophageal, colorectal and ovarian cancer and head and neck squamous cell carcinoma. On 14 September 2026 Perspective announced a clinical collaboration and supply agreement with Merck under which the trial is amended to add cohorts combining [212Pb]PSV359 with pembrolizumab in FAP-alpha-positive non-small cell lung cancer and colorectal cancer. That amendment is what puts an alpha-emitting radioligand into NSCLC, a tumour that radiopharmaceuticals have otherwise reached only as a diagnostic.\n\nPerspective guides initial phase 1/2a data in late 2026. Nothing has been published on activity in lung cancer, and the pipeline table still lists the programme's target disease simply as solid tumours.","status":"phase-1","asOf":"2026-09-23","links":[{"label":"Perspective Therapeutics: clinical collaboration and supply agreement with Merck to evaluate [212Pb]PSV359 with Keytruda in FAP-alpha positive solid tumours, 14 September 2026","url":"https://www.perspectivetherapeutics.com/pr/perspective-therapeutics-announces-clinical-collaboration-and-supply-agreement-with-merck-to-evaluate-212pbpsv359-in-combination-with-keytruda-pembrolizumab-in-fap-a-positive-solid-tumors"},{"label":"ClinicalTrials.gov NCT06710756: lead-212 PSV359 therapy for patients with solid tumours","url":"https://clinicaltrials.gov/study/NCT06710756"},{"label":"Perspective Therapeutics pipeline","url":"https://www.perspectivetherapeutics.com/pipeline/"}],"tags":["FAP","lead-212","alpha","NSCLC"],"related":["perspective-therapeutics","fap","fapi-pet","pb-212","pb-212-vmt-alpha-net","targeted-alpha-therapy","nsclc","merck","pembrolizumab"],"indications":["nsclc"],"sections":[],"technologies":[],"targets":["fap"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["nct06710756"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"code":"PSV359","modality":"Alpha-emitting radioligand (FAP-alpha targeted)","mechanism":"A small-molecule ligand for fibroblast activation protein alpha, the protease on the cancer-associated fibroblasts that build the stroma of most epithelial tumours, carrying lead-212 as the payload. Lead-212 decays through bismuth-212 to deliver an alpha particle, depositing its energy over a few cell diameters, so the dose lands on the stromal scaffold and the tumour cells packed against it rather than on distant marrow. The same targeting molecule labelled with lead-203 or gallium-68, designated PSV377, images FAP-alpha expression, so a patient can be selected on a scan before being treated.","approvals":[],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[]},"route":"/drugs/pb-212-psv359/","neighbours":{"company":[{"id":"merck","kind":"company","name":"Merck & Co. (MSD)","route":"/companies/merck/"},{"id":"perspective-therapeutics","kind":"company","name":"Perspective Therapeutics","route":"/companies/perspective-therapeutics/"}],"target":[{"id":"fap","kind":"target","name":"FAP","route":"/targets/fap/"}],"technology":[{"id":"fapi-pet","kind":"technology","name":"FAPI PET","route":"/technologies/fapi-pet/"},{"id":"targeted-alpha-therapy","kind":"technology","name":"Targeted alpha therapy","route":"/technologies/targeted-alpha-therapy/"}],"isotope":[{"id":"pb-212","kind":"isotope","name":"Lead-212","route":"/isotopes/pb-212/"}],"drug":[{"id":"pb-212-vmt-alpha-net","kind":"drug","name":"Lead-212 VMT-alpha-NET","route":"/drugs/pb-212-vmt-alpha-net/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"indication":[{"id":"nsclc","kind":"indication","name":"Non-small cell lung cancer","route":"/indications/nsclc/"}],"trial":[{"id":"nct06710756","kind":"trial","name":"Lead-212 PSV359 Therapy for Patients With Solid Tumors","route":"/trials/nct06710756/"}]}}