{"entity":{"id":"beta-psma-then-alpha-psma-rescue","kind":"pairing","name":"177Lu-PSMA-617 then 225Ac-PSMA rescue therapy","aka":[],"tldr":"When the standard radioactive prostate cancer treatment (177Lu-PSMA) stops working, some clinics switch to a more powerful alpha-particle version (225Ac-PSMA) as a rescue option. It can bring PSA down in about half of patients, but people who have already failed the beta treatment tend to respond less well and for a shorter time than those who have never had it.","summary":"225Ac-PSMA-617 or 225Ac-PSMA-I&T alpha-particle radioligand therapy is used, mainly outside the United States where actinium-225 is more accessible (for example in Germany), as salvage treatment for metastatic castration-resistant prostate cancer that has progressed after beta-emitting 177Lu-PSMA radioligand therapy (such as Pluvicto) plus prior androgen-receptor pathway inhibitors and taxane chemotherapy. Zacherl et al. (J Nucl Med 2021) reported the first dedicated series: of 14 patients treated with 225Ac-PSMA-I&T, 11 (79%) had previously received 177Lu-PSMA; 50% achieved a PSA decline of 50% or more, with median progression-free survival of 3.1 months and median overall survival of 7.7 months.\n\nA subsequent meta-analysis of retrospective 225Ac-PSMA-617 series (largely post-177Lu-PSMA patients) found pooled rates of 87% for any PSA decline and 66% for a PSA50 response, with pooled median overall survival of 12.5 months and progression-free survival of 9.1 months, and a molecular imaging response in 54% of patients — activity that the authors describe as clinically meaningful in a population that has exhausted other options, achieved with relatively low toxicity (xerostomia is the dominant, often dose-limiting, side effect; haematological toxicity is generally milder than with 177Lu-PSMA). A larger, more recent single-centre series (2025) similarly reported a median overall survival around 7 months in a mixed population, ranging up to 39 months in favourable cases.\n\nImportantly, multiple groups note that patients who progressed on 177Lu-PSMA before starting 225Ac-PSMA have inferior outcomes compared with alpha-therapy-naive patients (a 2022 series found a 45% versus 50% PSA50 rate, and a 2021 Ezziddin group series used 225Ac-PSMA as an 'augmentation' added to, rather than purely after, 177Lu-PSMA cycles, reporting median PSA-progression-free survival of 9.1 months and overall survival of 14.8 months). 225Ac-PSMA remains investigational (not FDA- or EMA-approved) and randomised trials comparing it against other post-177Lu-PSMA options are still needed; it is generally reserved for salvage use in patients with adequate marrow reserve who have exhausted approved options.","asOf":"2026-09-22","links":[{"label":"Zacherl et al., first clinical results for 225Ac-PSMA-I&T in advanced mCRPC, J Nucl Med 2021;62:669-674","url":"https://jnm.snmjournals.org/content/64/10/1574"},{"label":"Meta-analysis of efficacy and safety of 225Ac-PSMA-617 targeted alpha therapy (PMC8852230)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8852230/"},{"label":"Long-term safety and survival outcomes of 225Ac-PSMA (PMC11816130, 2025)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11816130/"}],"tags":["prostate cancer","alpha therapy","salvage therapy"],"related":["prostate-mcrpc","targeted-alpha-therapy","psma","clemens-kratochwil","uwe-haberkorn","lu-177","ac-225"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"a":"pluvicto","b":"ac225-psma","rationale":"Alpha particles deposit far more energy per track than beta particles and can still kill tumour cells that have become less responsive to 177Lu-PSMA, making 225Ac-PSMA a mechanistically plausible salvage option after beta-emitter progression.","evidence":"In a series of 14 patients (79% previously treated with 177Lu-PSMA), 225Ac-PSMA-I&T produced a PSA50 response in 50%, with median progression-free survival 3.1 months and overall survival 7.7 months (Zacherl et al., J Nucl Med 2021); a pooled meta-analysis of mostly post-177Lu-PSMA series found 66% PSA50 response and 12.5-month median overall survival, but response is consistently inferior to alpha-therapy-naive patients.","pairingType":"sequence"},"route":"/pairings/beta-psma-then-alpha-psma-rescue/","neighbours":{"indication":[{"id":"prostate-mcrpc","kind":"indication","name":"Metastatic castration-resistant prostate cancer","route":"/indications/prostate-mcrpc/"}],"technology":[{"id":"targeted-alpha-therapy","kind":"technology","name":"Targeted alpha therapy","route":"/technologies/targeted-alpha-therapy/"}],"target":[{"id":"psma","kind":"target","name":"PSMA","route":"/targets/psma/"}],"person":[{"id":"clemens-kratochwil","kind":"person","name":"Clemens Kratochwil","route":"/people/clemens-kratochwil/"},{"id":"uwe-haberkorn","kind":"person","name":"Uwe Haberkorn","route":"/people/uwe-haberkorn/"}],"isotope":[{"id":"ac-225","kind":"isotope","name":"Actinium-225","route":"/isotopes/ac-225/"},{"id":"lu-177","kind":"isotope","name":"Lutetium-177","route":"/isotopes/lu-177/"}],"drug":[{"id":"ac225-psma","kind":"drug","name":"Actinium-225 PSMA agents","route":"/drugs/ac225-psma/"},{"id":"pluvicto","kind":"drug","name":"Lutetium-177 vipivotide tetraxetan","route":"/drugs/pluvicto/"}]}}