Beta radioligand → alpha radioligand
After lutetium therapy stops working, an actinium version of the same drug can still produce responses.
Overview
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.
An alpha-emitting radioactive drug built on a PSMA-targeting antibody, rather than the small-molecule ligands used in existing PSMA therapies, was safe enough to move into further testing and shrank PSA in roughly a third to a half of heavily pre-treated men, including some whose cancer had already stopped responding to lutetium-177 PSMA therapy.
This was the first evidence, in two patients, that attaching a more powerful (alpha-emitting) form of radiation to the same PSMA-seeking molecule used in lutetium-177 PSMA therapy could produce a complete response even in prostate cancer that had already stopped responding to the beta-emitter version.
Similar pages
not linked directly; found by shared links- IdeaAlpha-emitting PSMA therapy at first metastatic diagnosis
Shares Alpha vs beta emitters, Actinium-225 PSMA agents, Lutetium-177 vipivotide tetraxetan, Targeted alpha therapy.
- PairingBeta PRRT → alpha PRRT
Shares Alpha vs beta emitters, Lutetium-177 dotatate, Targeted alpha therapy, Neuroendocrine tumours.
- TermRelative biological effectiveness (RBE)
Shares Alpha vs beta emitters, Targeted alpha therapy, Actinium-225, Radioligand therapy (beta emitters).
- BottleneckManufacturing cost and time for living and radioactive medicines
Shares Alpha vs beta emitters, Actinium-225 PSMA agents, Radiopharmaceutical roadmap: iodine → lutetium → actinium, Lutetium-177 dotatate.
- IdeaRecover legacy radium-226 sources worldwide as the feedstock for actinium-225
Shares Actinium-225 DOTATATE, Actinium-225 PSMA agents, Targeted alpha therapy, Actinium-225.
- TrialACTION-1
Shares Actinium-225 DOTATATE, Lutetium-177 dotatate, Targeted alpha therapy, Neuroendocrine tumours.
- Pairing177Lu-PSMA-617 then 225Ac-PSMA rescue therapy
Shares Actinium-225 PSMA agents, Lutetium-177 vipivotide tetraxetan, Targeted alpha therapy, Actinium-225.
- TermPRRT (peptide receptor radionuclide therapy)
Shares Alpha vs beta emitters, Lutetium-177 dotatate, Targeted alpha therapy, Neuroendocrine tumours.