{"doi":"10.1101/2020.07.24.220277","title":"A simple strategy to reduce the salivary gland and kidney uptake of PSMA targeting small molecule radiopharmaceuticals","abstract":"Abstract The past five years have seen an increasing acceptance of peptide-based prostate-specific membrane antigen (PSMA)-targeted radionuclide therapy (TRT) agents for treatment of metastatic castration-resistant prostate cancer (mCRPC), with [ 177 Lu]-DKFZ-PSMA-617 ([ 177 Lu]-PSMA-617) emerging as the leading candidate. [ 177 Lu]-PSMA-617 and other PSMA ligands have shown efficacy in reducing the tumor burden in mCRPC patients but irradiation to 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. Here, we report the effects of the addition of the cold PSMA ligand DKFZ-PSMA-11 (PSMA-11) on the uptake of [ 177 Lu]-PSMA-617 in tumor, salivary glands and kidneys. Groups of athymic nude mice (n = 4) bearing PC3-PIP (PSMA+) tumor xenografts were administered with [ 177 Lu]-PSMA-617 along with 0, 5, 100, 500, 1000 and 2000 pmoles of PSMA-11. Biodistribution studies 1 h post-administration revealed that [ 177 Lu]-PSMA-617 uptake in PSMA-expressing 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 kidney uptake values were 123.14±52.52, 132.31±47.4, 84.29±78.25, 2.12±1.88, 1.16±0.36, 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, 0.05±0.02 % ID/g, respectively. Thus, uptake of PSMA TRT agents in salivary gland and kidney can be substantially reduced without impact on tumor uptake by adding cold PSMA-11. Our data provides proof-of-concept and we propose that similar strategy be pursued in future clinical trials to prevent xerostomia and renal toxicity arising from [ 177 Lu]-PSMA-617.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":120029,"datarank":0.3958585994422889,"base_score":2.639057329615259,"endowment":2.639057329615259,"self_citation_contribution":0.3958585994422889,"citation_network_contribution":0.0,"self_endowment_contribution":0.3958585994422889,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.954,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":556347,"name":"Sang Gyu Lee","orcid":"0000-0003-4847-2421","position":1,"is_corresponding":false},{"id":556867,"name":"Katerina Jou","orcid":null,"position":2,"is_corresponding":false},{"id":368441,"name":"Goutam Chakraborty","orcid":"0000-0002-4387-2621","position":3,"is_corresponding":false},{"id":367141,"name":"Myrto Skafida","orcid":"0000-0001-7434-3282","position":4,"is_corresponding":false},{"id":354020,"name":"Scott T. Tagawa","orcid":"0000-0003-2777-8587","position":5,"is_corresponding":false},{"id":354019,"name":"Neil H. Bander","orcid":"0000-0003-4642-0759","position":6,"is_corresponding":false},{"id":255787,"name":"Heiko Schöder","orcid":"0000-0002-5170-4185","position":7,"is_corresponding":false},{"id":107710,"name":"Lisa Bodei","orcid":"0000-0001-6930-7383","position":8,"is_corresponding":false},{"id":438334,"name":"Neeta Pandit‐Taskar","orcid":"0000-0003-1551-2036","position":9,"is_corresponding":false},{"id":235762,"name":"Jason S. Lewis","orcid":"0000-0001-7065-4534","position":10,"is_corresponding":false},{"id":424346,"name":"Steven M. Larson","orcid":"0000-0002-6111-7507","position":11,"is_corresponding":false},{"id":354018,"name":"Joseph R. Osborne","orcid":"0000-0003-0232-5960","position":12,"is_corresponding":false},{"id":291557,"name":"Nagavarakishore Pillarsetty","orcid":"0000-0002-1750-7436","position":13,"is_corresponding":false},{"id":451222,"name":"Teja Kalidindi","orcid":"0000-0002-0210-0270","position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:14:13.002105Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}