[203Pb]Pb-PSV359

Overview

[203Pb]Pb-PSV359 is an investigational SPECT imaging agent that targets fibroblast activation protein alpha (FAP-α) and is being developed as the diagnostic companion to the targeted alpha therapy [212Pb]Pb-PSV359. It is currently being used for patient selection and dosimetry in an ongoing Phase 1/2a, image-guided alpha-therapy study in FAP-positive solid tumors (NCT06710756). As of October 2025, no human efficacy or safety results for [203Pb]Pb-PSV359 have been reported from clinical trials. (nasdaq.com)

Mechanism of action

• Target: FAP-α, expressed on cancer-associated fibroblasts and in some tumor cells across many epithelial cancers. PSV359 is a cyclic peptide discovered via high-throughput screening/phage display that binds human FAP with high affinity (reported Kd ~1.8 nM; Ki ~0.4 nM in preclinical studies). (globenewswire.com)
• Radiochemistry/theranostics: The peptide is conjugated to a Pb-specific chelator (PSC). Radiolabeling with Pb‑203 yields a SPECT tracer ([203Pb]Pb‑PSV359) that is chemically identical to the therapeutic [212Pb]Pb‑PSV359, enabling “see-then-treat” patient selection and dosimetry. Pb‑203/Pb‑212 form an elementally identical isotope pair optimized for matched imaging and therapy. (perspectivetherapeutics.com)

Early human imaging experience

First‑in‑human SPECT/CT images presented at EANM 2024 (oral presentation OP‑473) by an independent investigator showed, in three patients with FAP‑expressing cancers, strong tumor uptake, fast renal clearance, low normal‑organ background, and prolonged tumor retention after [203Pb]Pb‑PSV359 administration. These data were disclosed via the EANM 2024 program materials and company summaries. (globenewswire.com)

Clinical development status

• Trial design: A multicenter, open‑label Phase 1/2a study uses [203Pb]Pb‑PSV359 for SPECT imaging/dosimetry and patient selection, followed by treatment with [212Pb]Pb‑PSV359; primary objectives include safety/tolerability and recommended Phase 2 dose for the therapeutic agent, with antitumor activity assessed in expansion. Study start April 28, 2025; estimated primary completion January 31, 2028. (npcf.us)
• Recent updates: The first therapeutic patient was dosed on April 29, 2025; a second cohort (5.0 mCi [212Pb]Pb‑PSV359 q8 weeks, up to four doses) opened in October 2025. Imaging for selection is performed with [203Pb]Pb‑PSV359. (globenewswire.com)

Efficacy

• No clinical efficacy outcomes have been reported for [203Pb]Pb‑PSV359 (diagnostic) as of October 2025. Its role is patient selection and dosimetry for [212Pb]Pb‑PSV359; the therapeutic study is ongoing. (nasdaq.com)

Safety

• No clinical safety results specific to [203Pb]Pb‑PSV359 have been reported to date. The ongoing trial lists safety/tolerability of a single [203Pb]Pb‑PSV359 administration as a primary outcome. (npcf.us)

Further reading

• EANM 2024 oral presentation listing (OP‑473): Preclinical evaluation and first‑in‑human imaging of [203/212Pb]Pb‑PSV359. (Abstracts published via EJNMMI abstract book.) (globenewswire.com)
• Clinical trial record (overview and outcomes): NCT06710756 (Phase 1/2a image‑guided alpha‑therapy study of [203Pb]Pb‑PSV359 and [212Pb]Pb‑PSV359). (fdaaa.trialstracker.net)
• Company theranostics platform description (Pb‑203/Pb‑212 companion approach). (perspectivetherapeutics.com)
• Press updates on trial initiation and cohort expansion referencing [203Pb]Pb‑PSV359 use for patient selection. (globenewswire.com)

Notes: Most publicly available information for [203Pb]Pb‑PSV359 is from conference materials and company communications; peer‑reviewed, full‑length publications specific to PSV359 were not identified as of October 7, 2025. (globenewswire.com)

Last updated: Oct 2025