225Ac-PSMA-617 for PSMA-Targeted α-Radiation Therapy of Metastatic Castration-Resistant Prostate Cancer

J Nucl Med. 2016 Dec;57(12):1941-1944. doi: 10.2967/jnumed.116.178673. Epub 2016 Jul 7.


Prostate-specific membrane antigen (PSMA) is a promising target in prostate cancer. Recently, we started the first-in-human treatment with an α-radionuclide-labeled PSMA ligand. Although the case series is still ongoing, we here report in advance about two patients in highly challenging clinical situations who showed a complete response to 225Ac-PSMA-617 therapy.

Methods: 68Ga-PSMA-11 PET/CT validated the presence of the PSMA-positive tumor phenotype. A 100-kBq activity of 225Ac-PSMA-617 per kilogram of body weight was administered bimonthly. Prostate-specific antigen response and hematologic toxicity were measured at least every 4 wk. Restaging was performed with 68Ga-PSMA-11 PET/CT.

Results: Both patients experienced a prostate-specific antigen decline to below the measurable level and showed a complete response on imaging. No relevant hematologic toxicity was observed. Xerostomia was the only mentionable clinical side effect.

Conclusion: Targeted α-therapy with 225Ac-PSMA-617, although still experimental, obviously has strong potential to significantly benefit advanced-stage prostate cancer patients.

Keywords: 225Ac; PSMA; alpha-therapy.

Publication types

  • Case Reports

MeSH terms

  • Actinium*
  • Alpha Particles / therapeutic use*
  • Antigens, Surface / metabolism*
  • Beta Particles / therapeutic use
  • Dipeptides / therapeutic use*
  • Glutamate Carboxypeptidase II / metabolism*
  • Heterocyclic Compounds, 1-Ring / therapeutic use*
  • Humans
  • Lutetium / therapeutic use
  • Male
  • Neoplasm Metastasis
  • Positron Emission Tomography Computed Tomography
  • Prostatic Neoplasms, Castration-Resistant / diagnostic imaging
  • Prostatic Neoplasms, Castration-Resistant / metabolism
  • Prostatic Neoplasms, Castration-Resistant / pathology*
  • Prostatic Neoplasms, Castration-Resistant / radiotherapy*
  • Radioisotopes / therapeutic use*


  • Antigens, Surface
  • Dipeptides
  • Heterocyclic Compounds, 1-Ring
  • PSMA-617
  • Radioisotopes
  • Lutetium
  • FOLH1 protein, human
  • Glutamate Carboxypeptidase II
  • Actinium