Lead-212 PSV359
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.
Overview
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.
The 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.
Perspective 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.
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. Connects to FAP.
- PSMA / SSTR-positive cell
1.Lead-212 PSV359 binds FAP on the cancer cell or is taken up by it.
Trials
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Landmark trials
Latest papers
topQuery for this drug: (TITLE:"Lead-212 PSV359" OR ABSTRACT:"Lead-212 PSV359" OR TITLE:"PSV359" OR ABSTRACT:"PSV359" OR TITLE:"[212Pb]PSV359" OR ABSTRACT:"[212Pb]PSV359" OR TITLE:"PSV377 imaging analogue" OR ABSTRACT:"PSV377 imaging analogue") AND (radiopharmaceutical OR radioligand OR radionuclide OR theranostic OR "nuclear medicine" OR "molecular imaging" OR radiotracer OR scintigraphy OR cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Lead-212 PSV359, not a curated reading list.
Similar pages
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