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

   

Authors:	Kalidindi, T. M.; Lee, S. G.; Jou, K.; Chakraborty, G.; Skafida, M.; Tagawa, S. T.; Bander, N. H.; Schoder, H.; Bodei, L.; Pandit-Taskar, N.; Lewis, J. S.; Larson, S. M.; Osborne, J. R.; Pillarsetty, N. V. K.
Article Title:	A simple strategy to reduce the salivary gland and kidney uptake of PSMA-targeting small molecule radiopharmaceuticals
Abstract:	Purpose: 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. Methods: 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. Results: 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. Conclusion: 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. © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.
Keywords:	radiopharmaceuticals; mouse; animal; metabolism; animals; mice; quality of life; diagnostic imaging; prostatic neoplasms; membrane antigen; kidney; nude mouse; tissue distribution; mice, nude; prostate tumor; radiopharmaceutical agent; salivary gland; salivary glands; glutamate carboxypeptidase ii; antigens, surface; specific activity; single heterocyclic rings; heterocyclic compounds, 1-ring; kidneys; dose reduction; humans; human; male; psma trt; psma-617
Journal Title:	European Journal of Nuclear Medicine and Molecular Imaging
Volume:	48
Issue:	8
ISSN:	1619-7070
Publisher:	Springer
Date Published:	2021-07-01
Start Page:	2642
End Page:	2651
Language:	English
DOI:	10.1007/s00259-020-05150-w
PUBMED:	33495926
PROVIDER:	scopus
PMCID:	PMC10134681
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85099756202&doi=10.1007%2fs00259-020-05150-w&partnerID=40&md5=99892f8efc25893efdd5680d912560b3
Notes:	Article -- Export Date: 1 September 2021 -- Source: Scopus

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