Targeted alpha therapy
Like radioligand therapy but with alpha particles: far more destructive over a much shorter range, so single cells can be killed with less collateral damage.
Overview
Actinium-225 and lead-212 agents (225Ac-PSMA-617, 225Ac-DOTATATE/RYZ101, 212Pb-DOTAMTATE/AlphaMedix, 225Ac-FAP) are in phase 3. Radium-223 (Xofigo) is the only approved alpha emitter, for bone metastases. Isotope supply (TerraPower, Orano, ITM) is the binding constraint. Alpha therapy after beta failure produces responses in PSMA-refractory disease.
- PSMA / SSTR-positive cell
How it works
Alpha particles (4-9 MeV, <100 µm range) cause clustered double-strand breaks independent of oxygen and cell cycle.
- Overcomes beta resistance
- Kills micrometastases with minimal crossfire
- Ac-225 supply
- Daughter-nuclide redistribution (salivary, renal toxicity)
- Dosimetry difficult
Dependencies
Open the dependency map →Dependencies are what this technology cannot be delivered without: manufacturing steps, instruments, software, upstream methods. See its full chain on the map.
An alpha-particle version of neuroendocrine radioligand therapy that produced responses in over half of patients who had never had PRRT, with FDA Breakthrough designation.
An alpha-particle version of Lutathera for neuroendocrine tumours that have stopped responding to the beta version.
An antibody engineered to grab onto two markers found together on some solid tumours, but not on healthy cells, carries a powerful short-range radioactive payload into the tumour to try to destroy it.
Alpha-emitting PSMA drugs that produce responses even after Pluvicto fails, held back mainly by isotope supply.
A drug that homes to the scaffolding cells tumours build around themselves, carrying a radioactive metal that fires alpha particles over a very short range. A matching scan version shows first whether a patient's tumour has the target.
A drug that targets a marker on neuroendocrine tumour cells is being tested with two versions of a radioactive metal: one lets doctors see where the tumour is on a scan, and the other delivers a strong, short-range dose of radiation to kill the tumour cells.
Radium-223 was the first alpha-emitting drug ever approved (2013). It homes to bone like calcium and treats prostate cancer that has spread only to bone.
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 paper is a map of the radioactive-cancer-drug field at a pivotal moment, explaining to non-specialists and drug developers alike why these treatments work differently from chemotherapy and what needed to be fixed - supply, dosing science, regulation - before more of them could reach patients.
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.
Latest papers
topQuery for this technology: (TITLE:"targeted alpha therapy" OR ABSTRACT:"targeted alpha therapy" OR TITLE:"actinium-225" OR ABSTRACT:"actinium-225" OR TITLE:"225Ac" OR ABSTRACT:"225Ac" OR TITLE:"lead-212" OR ABSTRACT:"lead-212" OR TITLE:"212Pb" OR ABSTRACT:"212Pb"). Results are unfiltered search hits about Targeted alpha therapy, not a curated reading list.
Similar pages
not linked directly; found by shared links- TechnologyTROP2 PET
Shares Alpha radioligands after ADC failure and the tag frontier.
- IsotopeLutetium-177
Shares Full-Life Technologies, Alpha-9 Oncology, ARTBIO, Convergent Therapeutics.
- PersonUwe Haberkorn
Shares 177Lu-PSMA-617 then 225Ac-PSMA rescue therapy, 225Ac-PSMA-617 for PSMA-targeted alpha-radiation therapy of metastatic castration-resistant prostate cancer, Heidelberg University Hospital / NCT / DKFZ, A university cyclotron network with shared regulatory files for new tracers.
- CompanyBayer
Shares Oslo University Hospital, The Norwegian Radium Hospital, AlphaBreak (FPI-2265) & AcTION (225Ac-PSMA-617), Radium-223 dichloride, Actinium-225 supply.
- AgentLutetium-177 dotatate
Shares Lead-212 VMT-alpha-NET, Beta PRRT → alpha PRRT, ACTION-1, Beta radioligand → alpha radioligand.
- TermDosimetry
Shares Regional cyclotron hubs for actinium-225 with an agreed actinium-227 impurity limit, Alpha-emitter nanogenerators and daughter trapping, Auger-electron therapy, Alpha-emitting PSMA therapy at first metastatic diagnosis.
- IndicationMetastatic castration-resistant prostate cancer
Shares Full-Life Technologies, AdvanCell, Phase I dose-escalation study of 225Ac-J591, a PSMA-targeting alpha-emitting antibody, in mCRPC, 177Lu-PSMA-617 then 225Ac-PSMA rescue therapy.
- TechnologyCyclotron isotope production (F-18, Ga-68, Cu-64, Zr-89, At-211)
Shares Astatine-211 alpha therapy, IONETIX, Macropa chelation, Astatine-211.