# Targeted alpha therapy

Source: https://nuclide.cc/technologies/targeted-alpha-therapy/  
Nuclide record `targeted-alpha-therapy` (Technology). Data CC BY-NC 4.0, attribute "Data from Nuclide (nuclide.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Technology
- Status: phase-3
- Last checked: 2026-09-04
- Tags: frontier
- Principle: Alpha particles (4-9 MeV, <100 µm range) cause clustered double-strand breaks independent of oxygen and cell cycle.
- Strengths: Overcomes beta resistance; Kills micrometastases with minimal crossfire
- Limitations: Ac-225 supply; Daughter-nuclide redistribution (salivary, renal toxicity); Dosimetry difficult

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Targeted_alpha-particle_therapy
- Wikipedia: https://en.wikipedia.org/wiki/Targeted_alpha-particle_therapy

## Connected records

- technologies: [Actinium-225 supply: thorium stocks, accelerators and radium targets](https://nuclide.cc/technologies/actinium-225-supply/), [Alpha-emitter daughter redistribution ('free daughter' problem)](https://nuclide.cc/technologies/alpha-daughter-redistribution/), [Alpha-emitter nanogenerators and daughter trapping](https://nuclide.cc/technologies/alpha-nanogenerators/), [Astatine-211 alpha therapy](https://nuclide.cc/technologies/astatine-211-alpha-therapy/), [Auger-electron therapy](https://nuclide.cc/technologies/auger-electron-therapy/), [DOTA chelation](https://nuclide.cc/technologies/dota-chelation/), [Macropa chelation](https://nuclide.cc/technologies/macropa-chelation/), [Peptide receptor radionuclide therapy (PRRT)](https://nuclide.cc/technologies/prrt/), [Radio-antibody & radio-ADC](https://nuclide.cc/technologies/radioimmunotherapy/), [Radioligand dosimetry](https://nuclide.cc/technologies/radioligand-dosimetry/), [Radioligand plus DNA-repair inhibitor combinations](https://nuclide.cc/technologies/radionuclide-parp-combination/), [Radioligand therapy (beta emitters)](https://nuclide.cc/technologies/radioligand-therapy/), [Radiopharmacy and cyclotron networks](https://nuclide.cc/technologies/radiopharmacy-network/), [Therapeutic isotope supply chain (Mo-99, Lu-177, Ac-225)](https://nuclide.cc/technologies/therapy-isotope-supply-chain/)
- isotopes: [Actinium-225](https://nuclide.cc/isotopes/ac-225/), [Astatine-211](https://nuclide.cc/isotopes/at-211/), [Bismuth-213](https://nuclide.cc/isotopes/bi-213/), [Lead-212](https://nuclide.cc/isotopes/pb-212/), [Radium-223](https://nuclide.cc/isotopes/ra-223/), [Radium-224](https://nuclide.cc/isotopes/ra-224/), [Thorium-227](https://nuclide.cc/isotopes/th-227/)
- targets: [FAP](https://nuclide.cc/targets/fap/), [PSMA](https://nuclide.cc/targets/psma/), [Somatostatin receptor 2](https://nuclide.cc/targets/sstr2/)
- companies: [Abdera Therapeutics](https://nuclide.cc/companies/abdera-therapeutics/), [Actinium Pharmaceuticals](https://nuclide.cc/companies/actinium-pharmaceuticals/), [AdvanCell](https://nuclide.cc/companies/advancell/), [Aktis Oncology](https://nuclide.cc/companies/aktis-oncology/), [Alpha Tau Medical](https://nuclide.cc/companies/alpha-tau-medical/), [Alpha-9 Oncology](https://nuclide.cc/companies/alpha-9-oncology/), [Ariceum Therapeutics](https://nuclide.cc/companies/ariceum-therapeutics/), [ARTBIO](https://nuclide.cc/companies/artbio/), [Convergent Therapeutics](https://nuclide.cc/companies/convergent-therapeutics/), [Full-Life Technologies](https://nuclide.cc/companies/full-life-technologies/), [Fusion Pharmaceuticals (AstraZeneca)](https://nuclide.cc/companies/fusion-pharma/), [IONETIX](https://nuclide.cc/companies/ionetix/), [ITM Isotope Technologies Munich](https://nuclide.cc/companies/itm/), [Orano Med](https://nuclide.cc/companies/orano-med/), [Perspective Therapeutics](https://nuclide.cc/companies/perspective-therapeutics/), [RadioMedix](https://nuclide.cc/companies/radiomedix/), [Ratio Therapeutics](https://nuclide.cc/companies/ratio-therapeutics/), [RayzeBio (BMS)](https://nuclide.cc/companies/rayzebio/), [TerraPower Isotopes](https://nuclide.cc/companies/terrapower-isotopes/)
- indications: [Neuroendocrine tumours](https://nuclide.cc/indications/neuroendocrine/), [Prostate cancer](https://nuclide.cc/indications/prostate/), [Small-cell lung cancer](https://nuclide.cc/indications/sclc/), [Thyroid cancer](https://nuclide.cc/indications/thyroid/)
- drugs: [212Pb-DOTAMTATE](https://nuclide.cc/drugs/alphamedix/), [Actinium-225 DOTATATE](https://nuclide.cc/drugs/ryz101/), [Actinium-225 FPI-2068](https://nuclide.cc/drugs/ac-225-fpi-2068/), [Actinium-225 PSMA agents](https://nuclide.cc/drugs/ac225-psma/), [Lead-212 PSV359](https://nuclide.cc/drugs/pb-212-psv359/), [Lead-212 VMT-alpha-NET](https://nuclide.cc/drugs/pb-212-vmt-alpha-net/), [Radium-223 dichloride](https://nuclide.cc/drugs/radium-223/)
- institutions: [European Association of Nuclear Medicine](https://nuclide.cc/institutions/eanm/), [Heidelberg University Hospital / NCT / DKFZ](https://nuclide.cc/institutions/heidelberg-nct/), [Institut de Cancérologie de l'Ouest (ICO)](https://nuclide.cc/institutions/ico-angers-nantes/), [Oslo University Hospital, The Norwegian Radium Hospital](https://nuclide.cc/institutions/oslo-radium-hospital/), [QST Hospital (National Institutes for Quantum Science and Technology)](https://nuclide.cc/institutions/qst-hospital/), [Society of Nuclear Medicine and Molecular Imaging](https://nuclide.cc/institutions/snmmi/)
- terms: [Alpha vs beta emitters](https://nuclide.cc/terms/alpha-vs-beta/), [Linear energy transfer (LET)](https://nuclide.cc/terms/linear-energy-transfer/), [PRRT (peptide receptor radionuclide therapy)](https://nuclide.cc/terms/prrt-term/), [Relative biological effectiveness (RBE)](https://nuclide.cc/terms/relative-biological-effectiveness/), [Theranostics](https://nuclide.cc/terms/theranostics/)
- trials: [ACTION-1](https://nuclide.cc/trials/action-1/), [AlphaBreak (FPI-2265) & AcTION (225Ac-PSMA-617)](https://nuclide.cc/trials/alphabreak/), [ALPHAMEDIX-02](https://nuclide.cc/trials/alphamedix-02/), [ALSYMPCA](https://nuclide.cc/trials/alsympca/)
- pairings: [177Lu-PSMA-617 then 225Ac-PSMA rescue therapy](https://nuclide.cc/pairings/beta-psma-then-alpha-psma-rescue/), [Beta PRRT → alpha PRRT](https://nuclide.cc/pairings/prrt-then-alpha-net/), [Beta radioligand → alpha radioligand](https://nuclide.cc/pairings/beta-then-alpha/)
- roadmaps: [Alpha-emitter roadmap: radium-223 → 225Ac-PSMA-617 → a phase 3 pipeline](https://nuclide.cc/roadmaps/alpha-therapy-roadmap/), [PSMA theranostics roadmap: antigen discovery → PSMA PET → 177Lu-PSMA-617 → earlier lines and alpha](https://nuclide.cc/roadmaps/psma-theranostics-roadmap/), [Radiopharmaceutical roadmap: iodine → lutetium → actinium](https://nuclide.cc/roadmaps/radiopharma-roadmap/), [SSTR theranostics roadmap: octreotide scintigraphy → 68Ga-DOTATATE → 177Lu-DOTATATE → alpha](https://nuclide.cc/roadmaps/sstr-theranostics-roadmap/)
- ideas: [A global medical isotope supply observatory with forecasts and shortage alerts](https://nuclide.cc/ideas/idea-reg-isotope-supply-observatory/), [A university cyclotron network with shared regulatory files for new tracers](https://nuclide.cc/ideas/idea-fund-academic-radiopharma-pipeline/), [Alpha radioligands after ADC failure](https://nuclide.cc/ideas/idea-alpha-after-adc/), [Alpha-emitting PSMA therapy at first metastatic diagnosis](https://nuclide.cc/ideas/idea-alpha-first-mhspc/), [CAIX theranostics: 89Zr-girentuximab PET and 177Lu/225Ac-girentuximab therapy](https://nuclide.cc/ideas/idea-caix-theranostics/), [FAP theranostics as a pan-cancer stromal strategy](https://nuclide.cc/ideas/idea-fap-theranostics-pancancer/), [Fund alpha emitters beyond actinium-225: lead-212, terbium-149 and astatine-211](https://nuclide.cc/ideas/idea-reg-alpha-emitter-portfolio/), [Pretargeted alpha radioimmunotherapy](https://nuclide.cc/ideas/idea-pretargeted-alpha-therapy/), [Recover legacy radium-226 sources worldwide as the feedstock for actinium-225](https://nuclide.cc/ideas/idea-reg-legacy-radium-recovery-ac225/), [Regional cyclotron hubs for actinium-225 with an agreed actinium-227 impurity limit](https://nuclide.cc/ideas/idea-reg-ac225-accelerator-pharmacopoeia/)
- people: [Clemens Kratochwil](https://nuclide.cc/people/clemens-kratochwil/)
- bottlenecks: [Actinium-225 supply](https://nuclide.cc/bottlenecks/b-ac225-supply/), [Clinical trial capacity for radioligand therapy](https://nuclide.cc/bottlenecks/b-rlt-trial-capacity/), [Manufacturing cost and time for living and radioactive medicines](https://nuclide.cc/bottlenecks/b-manufacturing-cell-therapy/)
- fronts: [Targeted alpha therapy](https://nuclide.cc/fronts/f-alpha-therapy/)
- key papers: [225Ac-PSMA-617 for PSMA-targeted alpha-radiation therapy of metastatic castration-resistant prostate cancer](https://nuclide.cc/key-papers/paper-kratochwil-ac225-psma-jnm-2016/), [Phase I dose-escalation study of 225Ac-J591, a PSMA-targeting alpha-emitting antibody, in mCRPC](https://nuclide.cc/key-papers/paper-tagawa-ac225-j591-jco-2024/), [Radiopharmaceutical therapy in cancer: clinical advances and challenges](https://nuclide.cc/key-papers/paper-sgouros-tat-review-nat-rev-2020/)

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