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J Nucl Med. 2016 Aug;57(8):1170-6. doi: 10.2967/jnumed.115.171397. Epub 2016 Mar 16.

PSMA-Targeted Radionuclide Therapy of Metastatic Castration-Resistant Prostate Cancer with 177Lu-Labeled PSMA-617.

Author information

1
Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany clemens.kratochwil@med.uni-heidelberg.de.
2
Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center (dkfz), Heidelberg, Germany.
3
Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany.
4
Division of Radiopharmaceutical Chemistry, German Cancer Research Center (dkfz), Heidelberg, Germany; and.
5
ABX-CRO, Dresden, Germany.

Abstract

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.

KEYWORDS:

177Lu; PSMA; castration-resistant prostate cancer; dosimetry; pharmacokinetics; radionuclide therapy

PMID:
26985056
DOI:
10.2967/jnumed.115.171397
[Indexed for MEDLINE]
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