Targeted α-Therapy of Metastatic Castration-Resistant Prostate Cancer with 225Ac-PSMA-617: Dosimetry Estimate and Empiric Dose Finding
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The aim of this study was to develop a treatment protocol for 225Ac-PSMA-617 α-radiation therapy in advanced-stage, metastatic castration-resistant prostate cancer patients with prostate-specific membrane antigen (PSMA)–positive tumor phenotype. Methods: A dosimetry estimate was calculated on the basis of time–activity curves derived from serially obtained 177Lu-PSMA-617 scans extrapolated to the physical half-life of 225Ac, assuming instant decay of unstable daughter nuclides. Salvage therapies empirically conducted with 50 (n = 4), 100 (n = 4), 150 (n = 2), and 200 kBq/kg (n = 4) of 225Ac-PSMA-617 were evaluated retrospectively regarding toxicity and treatment response. Eight of 14 patients received further cycles in either 2- or 4-mo intervals with identical or deescalated activities. Results: Dosimetry estimates for 1 MBq of 225Ac-PSMA-617 assuming a relative biologic effectiveness of 5 revealed mean doses of 2.3 Sv for salivary glands, 0.7 Sv for kidneys, and 0.05 Sv for red marrow that are composed of 99.4% α, 0.5% β, and 0.1% photon radiation, respectively. In clinical application, severe xerostomia became the dose-limiting toxicity if treatment activity exceeded 100 kBq/kg per cycle. At 100 kBq/kg, the duration of prostate-specific antigen decline was less than 4 mo, but if therapy was repeated every 2 mo patients experienced additive antitumor effects. Treatment activities of 50 kBq/kg were without toxicity but induced insufficient antitumor response in these high-tumor-burden patients. Remarkable antitumor activity by means of objective radiologic response or tumor marker decline was observed in 9 of 11 evaluable patients. Conclusion: For advanced-stage patients, a treatment activity of 100 kBq/kg of 225Ac-PSMA-617 per cycle repeated every 8 wk presents a reasonable trade-off between toxicity and biochemical response.
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Current clinical TAT research relies greatly on indirect approximation by extrapolating pre-existing 177Lu-labeled pharmaceuticals.
“Thus, current clinical TAT research relies greatly on indirect approximation by extrapolating pre-existing 177Lu-labeled pharmaceuticals (84, 112, 113).”
From Alpha-peptide receptor radionuclide therapy using actinium-225 labeled somatostatin receptor agonists and antagonists (2022) · cites this paper as [84]
A low probability of γ-emission and overlapping Bremsstrahlung due to β-emitters in the 225Ac decay chain preclude simultaneous treatment and dosimetry measurement in a clinical setting.
“However, a low probability of γ-emission and overlapping Bremsstrahlung due to β-emitters in the 225Ac decay chain preclude simultaneous treatment and dosimetry measurement in a clinical setting (84).”
From Alpha-peptide receptor radionuclide therapy using actinium-225 labeled somatostatin receptor agonists and antagonists (2022) · cites this paper as [84]
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- Authors
- Kratochwil, C., Bruchertseifer, F., Rathke, H., Bronzel, M., Apostolidis, C., Weichert, W., Haberkorn, U., Giesel, F. L., & Morgenstern, A.
- Affiliations
- University Hospital Heidelberg (DE)
- European Commission (BE)
- ABX-CRO Advanced Pharmaceutical Services (Germany) (DE)
- Pathologisches Institut (DE)
- German Cancer Research Center (DE)
- ORCID
- Venue
- Journal of Nuclear Medicine
- Publisher
- Society of Nuclear Medicine
- Published
- 2017-04-13
- Volume
- 58
- Issue
- 10
- Pages
- 1624-1631
- ISSN
- 0161-5505 (ISSN-L)
- 2159-662X
- OpenAlex
- W2606187374
- Cited by
- 505
- References
- 31
- Citations by year
- 2026: 35 · 2025: 60 · 2024: 48 · 2023: 36 · 2022: 53 · 2021: 83 · 2020: 57 · 2019: 61 · 2018: 57 · 2017: 14 · 2016: 1
- FWCI
- 39.13
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Nuclear Medicine (publishedVersion)
- PubMed (publishedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Joint Research Centre (European Commission) (submittedVersion)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Keywords
- metastatic castration-resistant prostate cancer, dosimetry, 177Lu-PSMA-617, xerostomia, salvage therapy, PSA response, treatment toxicity
- MeSH terms
- Actinium, Aged, Alpha Particles, Dipeptides, Heterocyclic Compounds, 1-Ring, Humans, Male, Middle Aged, Neoplasm Metastasis, Radiometry, Radiotherapy Dosage, Prostate-Specific Antigen, Prostatic Neoplasms, Castration-Resistant
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