# PSMA theranostics roadmap: antigen discovery → PSMA PET → 177Lu-PSMA-617 → earlier lines and alpha

Source: https://nuclide.cc/roadmaps/psma-theranostics-roadmap/  
Nuclide record `psma-theranostics-roadmap` (Roadmap). Data CC BY-NC 4.0, attribute "Data from Nuclide (nuclide.cc)"; commercial use needs a licence.

## TL;DR

Prostate-specific membrane antigen was found on prostate cancer cells in 1987. It took until 2020-2022 for scans and treatments that target it to reach approval, but once they did, PSMA PET and Pluvicto changed how metastatic prostate cancer is staged and treated, and the same target is now being tried earlier in the disease and with more powerful alpha particles.

## Summary

Prostate-specific membrane antigen (PSMA) was first identified in 1987 when Horoszewicz and Murphy raised the monoclonal antibody 7E11-C5 against the LNCaP prostate cancer cell line; Heston and Fair's group at Memorial Sloan Kettering cloned the PSMA gene in 1993. The first PSMA-targeted imaging agent to reach approval, indium-111 capromab pendetide (ProstaScint), was approved by the FDA on 28 October 1996, but bound only an intracellular epitope and had limited clinical impact.

The modern era begins with small-molecule PSMA ligands: Eder and colleagues at the German Cancer Research Center (DKFZ) Heidelberg synthesised the gallium-68-labelled HBED-CC compound that became PSMA-11 in 2012, building on first-in-human work from 2011. It took until 1 December 2020 for the FDA to approve 68Ga-PSMA-11 (jointly, as separate applications from UCSF and UCLA), the first PSMA PET agent approved in the US, followed by the first commercially distributable PSMA PET agent, Pylarify (piflufolastat F 18), on 26 May 2021. On the therapy side, Kratochwil's Heidelberg group had already shown in 2016 that the corresponding alpha-emitting ligand, 225Ac-PSMA-617, could produce complete responses; the beta-emitting version, 177Lu-PSMA-617 (Pluvicto), was approved by the FDA on 23 March 2022 for post-chemotherapy mCRPC, based on the VISION trial (a 38% reduction in risk of death).

The label then moved earlier: on 28 March 2025 the FDA expanded Pluvicto's indication, based on the PSMAfore trial, to PSMA-positive mCRPC patients who have progressed on one androgen receptor pathway inhibitor and are considered appropriate to delay chemotherapy, removing the prior-taxane requirement and roughly tripling the eligible US population. The alpha-emitting analogue of Pluvicto, 225Ac-PSMA-617 (AAA817, Novartis), and a second alpha PSMA ligand, FPI-2265 (225Ac-PSMA-I&T, Fusion Pharmaceuticals), are both now in phase 3 programmes for patients whose disease has progressed on 177Lu-PSMA, the next planned step in the sequence.

## Fields

- Kind: Roadmap
- Last checked: 2026-09-22

## Sources

- FDA: Ga 68 PSMA-11 injection approval (UCSF/UCLA), December 2020: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212643Orig1s000Approv.pdf
- Lantheus: FDA approval of Pylarify, May 2021: https://investor.lantheus.com/news-releases/news-release-details/lantheus-receives-us-fda-approval-pylarifyr-piflufolastat-f-18
- FDA: Pluvicto (lutetium Lu 177 vipivotide tetraxetan) approval summary, March 2022 (PMC): https://pmc.ncbi.nlm.nih.gov/articles/PMC10159870/
- FDA: Pluvicto label expansion based on PSMAfore, March 2025: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-expands-pluvictos-metastatic-castration-resistant-prostate-cancer-indication

## Connected records

- isotopes: [Actinium-225](https://nuclide.cc/isotopes/ac-225/), [Fluorine-18](https://nuclide.cc/isotopes/f-18/), [Gallium-68](https://nuclide.cc/isotopes/ga-68/), [Indium-111](https://nuclide.cc/isotopes/in-111/), [Lutetium-177](https://nuclide.cc/isotopes/lu-177/)
- indications: [Metastatic castration-resistant prostate cancer](https://nuclide.cc/indications/prostate-mcrpc/), [Prostate cancer](https://nuclide.cc/indications/prostate/)
- technologies: [Lutetium-177 radioligand therapy](https://nuclide.cc/technologies/lu177-radioligand-therapy/), [PSMA PET](https://nuclide.cc/technologies/psma-pet/), [Targeted alpha therapy](https://nuclide.cc/technologies/targeted-alpha-therapy/)
- targets: [PSMA](https://nuclide.cc/targets/psma/)
- drugs: [177Lu-PSMA-I&T](https://nuclide.cc/drugs/lu177-psma-it/), [Actinium-225 PSMA agents](https://nuclide.cc/drugs/ac225-psma/), [Gallium-68 gozetotide (PSMA-11)](https://nuclide.cc/drugs/ga68-psma-11/), [Illuccix (kit for Ga-68 gozetotide)](https://nuclide.cc/drugs/illuccix/), [Locametz (kit for Ga-68 gozetotide)](https://nuclide.cc/drugs/locametz/), [Lutetium-177 vipivotide tetraxetan](https://nuclide.cc/drugs/pluvicto/), [Piflufolastat F-18 / Pylarify TruVu](https://nuclide.cc/drugs/pylarify/)
- trials: [AlphaBreak (FPI-2265) & AcTION (225Ac-PSMA-617)](https://nuclide.cc/trials/alphabreak/), [PSMAfore](https://nuclide.cc/trials/psmafore/), [VISION](https://nuclide.cc/trials/vision/)
- people: [Clemens Kratochwil](https://nuclide.cc/people/clemens-kratochwil/), [Michael Hofman](https://nuclide.cc/people/hofman-michael/), [Michael J. Morris](https://nuclide.cc/people/michael-morris/), [Thomas A. Hope](https://nuclide.cc/people/thomas-hope/), [Uwe Haberkorn](https://nuclide.cc/people/uwe-haberkorn/)
- key papers: [proPSMA: PSMA PET-CT versus conventional imaging for staging high-risk prostate cancer](https://nuclide.cc/key-papers/paper-propsma-hofman-lancet-2020/), [VISION: lutetium-177 PSMA-617 radioligand therapy extends survival in advanced prostate cancer](https://nuclide.cc/key-papers/paper-vision-nejm-2021/)
- ideas: [Alpha-emitting PSMA therapy at first metastatic diagnosis](https://nuclide.cc/ideas/idea-alpha-first-mhspc/), [PSMA-PET-guided metastasis-directed therapy as a curative strategy in oligorecurrent prostate cancer](https://nuclide.cc/ideas/idea-psma-pet-guided-mdt/), [Qualify PSMA PET tumour volume as a validated imaging biomarker](https://nuclide.cc/ideas/idea-tr2-psma-volume-qualification/)

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