PSMA-Targeted Radionuclide Therapy of Metastatic Castration-Resistant Prostate Cancer with 177Lu-Labeled PSMA-617
Open accessAbstract
UNLABELLED: Prostate-specific membrane antigen (PSMA) is an excellent target for radionuclide therapy of metastasized castration-resistant prostate cancer (mCRPC). Besides high affinity and long tumor retention, the DOTA-conjugated ligand PSMA-617 has low kidney uptake, making it an excellent choice for therapeutic application. We retrospectively report our experience with (177)Lu-PSMA-617-targeted radionuclide therapy in a case series of mCRPC patients resistant to other treatments. METHODS: Patients with PSMA-positive tumor phenotypes were selected by molecular imaging. Thirty patients received 1-3 cycles of (177)Lu-PSMA-617. During therapy, pharmacokinetics and radiation dosimetry were evaluated. Blood cell count was checked every 2 wk after the first and every 4 wk after succeeding cycles. Prostate-specific antigen (PSA) was determined every 4 wk. Radiologic restaging was performed after 3 cycles. RESULTS: Twenty-one of 30 patients had a PSA response; in 13 of 30 the PSA decreased more than 50%. After 3 cycles, 8 of 11 patients achieved a sustained PSA response (>50%) for over 24 wk, which also correlated with radiologic response (decreased lesion number and size). Normally, acute hematotoxicity was mild. Diffuse bone marrow involvement was a risk factor for higher grade myelosuppression but could be identified by PSMA imaging in advance. Xerostomia, nausea, and fatigue occurred sporadically (<10%). Clearance of non-tumor-bound tracer was predominantly renal and widely completed by 48 h. Safety dosimetry revealed kidney doses of approximately 0.75 Gy/GBq, red marrow doses of 0.03 Gy/GBq, and salivary gland doses of 1.4 Gy/GBq, irrespective of tumor burden and consistent on subsequent cycles. Mean tumor-absorbed dose ranged from 6 to 22 Gy/GBq during cycle 1. CONCLUSION: (177)Lu-PSMA-617 is a promising new option for therapy of mCRPC and deserves more attention in larger prospective trials.
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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 [112]
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- Authors
- Kratochwil, C., Giesel, F. L., Stefanova, M., Benešová, M., Bronzel, M., Afshar-Oromieh, A., Mier, W., Eder, M., Kopka, K., & Haberkorn, U.
- Affiliations
- University Hospital Heidelberg (DE)
- German Cancer Research Center (DE)
- ABX-CRO Advanced Pharmaceutical Services (Germany) (DE)
- ORCID
- Venue
- Journal of Nuclear Medicine
- Publisher
- Society of Nuclear Medicine
- Published
- 2016-03-16
- Volume
- 57
- Issue
- 8
- Pages
- 1170-1176
- ISSN
- 0161-5505 (ISSN-L)
- 2159-662X
- OpenAlex
- W2304896218
- Cited by
- 636
- References
- 32
- Citations by year
- 2026: 45 · 2025: 58 · 2024: 60 · 2023: 51 · 2022: 58 · 2021: 93 · 2020: 56 · 2019: 61 · 2018: 58 · 2017: 57 · 2016: 39
- FWCI
- 62.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Nuclear Medicine (publishedVersion)
- PubMed (publishedVersion)
- 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 › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Keywords
- castration-resistant prostate cancer, metastatic prostate cancer, PSMA-617, lutetium-177, PSMA radioligand therapy, prostate-specific membrane antigen, radiation dosimetry, hematologic toxicity, bone marrow involvement, xerostomia, PSA response, radiological response
- MeSH terms
- Aged, Aged, 80 and over, Antigens, Surface, Dipeptides, Heterocyclic Compounds, 1-Ring, Humans, Lymphatic Metastasis, Male, Middle Aged, Biomarkers, Tumor, Treatment Outcome, Prostate-Specific Antigen, Radiopharmaceuticals, Glutamate Carboxypeptidase II, Prostatic Neoplasms, Castration-Resistant
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