{"entity":{"id":"beta-then-alpha","kind":"pairing","name":"Beta radioligand → alpha radioligand","aka":[],"tldr":"After lutetium therapy stops working, an actinium version of the same drug can still produce responses.","summary":"This sequence pairing follows Radioligand therapy (beta emitters) with Targeted alpha therapy using the same targeting molecule: after lutetium stops working, an actinium version of the same drug can still produce responses. Alpha particles cause oxygen-independent clustered DNA damage that beta-resistant, hypoxic or small-volume disease cannot repair, as explained in the Alpha vs beta emitters entry. In Prostate cancer, Actinium-225 PSMA agents after Lutetium-177 vipivotide tetraxetan produced PSA responses in retrospective series, and phase 3 trials (AcTION, AlphaBreak) are ongoing. In Neuroendocrine tumours, Actinium-225 DOTATATE (RYZ101) is being tested in ACTION-1 after Lutetium-177 dotatate, so the evidence is retrospective and phase 1/2 with phase 3 pending.","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov NCT06402331: AlphaBreak (FPI-2265) & AcTION (225Ac-PSMA-617)","url":"https://clinicaltrials.gov/study/NCT06402331"}],"tags":[],"related":["lu-177","ac-225"],"indications":["prostate","neuroendocrine"],"sections":[],"technologies":[],"targets":[],"drugs":["pluvicto","ac225-psma","lutathera","ryz101"],"companies":[],"institutions":[],"pathways":[],"terms":["alpha-vs-beta"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"a":"radioligand-therapy","b":"targeted-alpha-therapy","rationale":"Alpha particles cause oxygen-independent clustered DNA damage that beta-resistant, hypoxic, or small-volume disease cannot repair.","evidence":"Retrospective and phase 1/2; phase 3 pending.","pairingType":"sequence"},"route":"/pairings/beta-then-alpha/","neighbours":{"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/"}],"indication":[{"id":"neuroendocrine","kind":"indication","name":"Neuroendocrine tumours","route":"/indications/neuroendocrine/"},{"id":"prostate","kind":"indication","name":"Prostate cancer","route":"/indications/prostate/"}],"drug":[{"id":"ryz101","kind":"drug","name":"Actinium-225 DOTATATE","route":"/drugs/ryz101/"},{"id":"ac225-psma","kind":"drug","name":"Actinium-225 PSMA agents","route":"/drugs/ac225-psma/"},{"id":"lutathera","kind":"drug","name":"Lutetium-177 dotatate","route":"/drugs/lutathera/"},{"id":"pluvicto","kind":"drug","name":"Lutetium-177 vipivotide tetraxetan","route":"/drugs/pluvicto/"}],"term":[{"id":"alpha-vs-beta","kind":"term","name":"Alpha vs beta emitters","route":"/terms/alpha-vs-beta/"}],"technology":[{"id":"radioligand-therapy","kind":"technology","name":"Radioligand therapy (beta emitters)","route":"/technologies/radioligand-therapy/"},{"id":"targeted-alpha-therapy","kind":"technology","name":"Targeted alpha therapy","route":"/technologies/targeted-alpha-therapy/"}],"roadmap":[{"id":"radiopharma-roadmap","kind":"roadmap","name":"Radiopharmaceutical roadmap: iodine → lutetium → actinium","route":"/roadmaps/radiopharma-roadmap/"}],"paper":[{"id":"paper-kratochwil-ac225-psma-jnm-2016","kind":"paper","name":"225Ac-PSMA-617 for PSMA-targeted alpha-radiation therapy of metastatic castration-resistant prostate cancer","route":"/key-papers/paper-kratochwil-ac225-psma-jnm-2016/"},{"id":"paper-tagawa-ac225-j591-jco-2024","kind":"paper","name":"Phase I dose-escalation study of 225Ac-J591, a PSMA-targeting alpha-emitting antibody, in mCRPC","route":"/key-papers/paper-tagawa-ac225-j591-jco-2024/"}]}}