A simple strategy to reduce the salivary gland and kidney uptake of PSMA-targeting small molecule radiopharmaceuticals

Autor:	Myrto Skafida, Scott T. Tagawa, Naga Vara Kishore Pillarsetty, Neil H. Bander, Neeta Pandit-Taskar, Teja Kalidindi, Joseph R. Osborne, Sang-Gyu Lee, Steven M. Larson, Jason S. Lewis, Heiko Schöder, Katerina Jou, Goutam Chakraborty, Lisa Bodei
Rok vydání:	2021
Předmět:	Glutamate Carboxypeptidase II Biodistribution Mice Nude Peptide Pharmacology Kidney urologic and male genital diseases Salivary Glands Article 030218 nuclear medicine & medical imaging Heterocyclic Compounds 1-Ring Mice 03 medical and health sciences Prostate cancer 0302 clinical medicine medicine Animals Humans Tissue Distribution Radiology Nuclear Medicine and imaging chemistry.chemical_classification Salivary gland Tumor Protein Translationally-Controlled 1 General Medicine medicine.disease Small molecule medicine.anatomical_structure chemistry 030220 oncology & carcinogenesis Antigens Surface Toxicity Quality of Life Specific activity Radiopharmaceuticals
Zdroj:	Eur J Nucl Med Mol Imaging
ISSN:	1619-7089 1619-7070
Popis:	Peptide-based prostate-specific membrane antigen (PSMA) targeted radionuclide therapy (TRT) agent [177Lu]-PSMA-617 has emerged as leading TRT candidate for treatment of castration-resistant prostate cancer (mCRPC). [177Lu]-PSMA-617 and other small molecule–based PSMA ligands have shown efficacy in reducing the tumor burden in mCRPC patients but irradiation to the salivary gland and kidneys is a concern and dose-limiting factor. Therefore, methods to reduce non-target organ toxicity are needed to safely treat patients and preserve their quality of life. Herein, we report that addition of cold PSMA ligand PSMA-11 can aid in reducing the uptake of [177Lu]-PSMA-617 in the salivary glands and kidneys. Groups of athymic nude mice (n = 4) bearing PC3-PIP (PSMA+) tumor xenografts were administered with [177Lu]-PSMA-617 along with 0, 5, 100, 500, 1000, and 2000 pmoles of PSMA-11 and biodistribution studies were performed at 1 h. Biodistribution studies at 1 h post-administration revealed that [177Lu]-PSMA-617 uptake in PC3-PIP tumors was 21.71 ± 6.13, 18.7 ± 2.03, 26.44 ± 2.94, 16.21 ± 3.5, 13.52 ± 3.68, and 12.03 ± 1.96 %ID/g when 0, 5, 100, 500, 1000, and 2000 pmoles of PSMA-11 were added, respectively. Corresponding uptake values in kidney were 123.14 ± 52.52, 132.31 ± 47.4, 84.29 ± 78.25, 2.12 ± 1.88, 1.16 ± 0.36, and 0.64 ± 0.23 %ID/g, respectively. Corresponding salivary gland uptake values were 0.48 ± 0.11, 0.45 ± 0.15, 0.38 ± 0.3, 0.08 ± 0.03, 0.09 ± 0.07, and 0.05 ± 0.02 % ID/g, respectively. The uptake of [177Lu]-PSMA-617 in the salivary gland and kidney can be substantially reduced without significantly impacting tumor uptake by adding cold PSMA-11.
Databáze:	OpenAIRE
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