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

Abstract

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.

• Authors: Clemens Kratochwil, Frank Bruchertseifer, Frederik L Giesel, Mirjam Weis, Frederik A Verburg, Felix Mottaghy, Klaus Kopka, Christos Apostolidis, Uwe Haberkorn, Alfred Morgenstern
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 57 Issue 12 Pg. 1941-1944 (Dec 2016) ISSN: 1535-5667 [Electronic] United States
• PMID: 27390158 (Publication Type: Case Reports, Journal Article)
• Copyright: © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Chemical References

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

Topics

• 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
• Prostate-Specific Antigen
• Prostatic Neoplasms, Castration-Resistant (diagnostic imaging, metabolism, pathology, radiotherapy)
• Radioisotopes (therapeutic use)