{"doi":"10.2967/jnumed.125.269751","title":"Evaluation of <sup>134</sup>Ce/<sup>134</sup>La-PSMA-617 for PET Imaging and Auger Electron Therapy of Prostate Cancer","abstract":"The <sup>134</sup>Ce/<sup>134</sup>La radionuclide pair has been proposed as a PET imaging surrogate for targeted α-radiotherapeutics. <sup>134</sup>Ce decays to <sup>134</sup>La via electron capture, emitting Auger electrons (AEs), which could be used for targeted radionuclide therapy. Additionally, the positron emission during this transition enables PET imaging, making <sup>134</sup>Ce/<sup>134</sup>La a promising theranostic pair for prostate cancer. In this work, we investigated the potential of <sup>134</sup>Ce for AE capture therapy using prostate-specific membrane antigen (PSMA)-617 for targeted radionuclide delivery. <b>Methods:</b> Radiolabeling of [<sup>134</sup>Ce]Ce-PSMA-617 proceeded as previously described, and C18 cartridge purification was optimized. In vitro, cell-binding and toxicity assays were performed on PSMA-positive PC3 PIP cells. In vivo PET imaging and ex vivo biodistribution studies were conducted on mice bearing dual PSMA-positive PC3 PIP and PSMA-negative PC3 flu tumor xenografts at various time points ranging from 1 to 72 h after injection. Additionally, an in&nbsp;vivo single-dose-treatment study was performed using 37- and 111-MBq doses in nude mice with PC3 PIP tumor xenografts. <b>Results:</b> PSMA-617 was successfully radiolabeled with <sup>134</sup>Ce/<sup>134</sup>La and purified using the C18 cartridge method, achieving high molar activity (21.02 ± 0.11 MBq/nmol). Stability studies showed more than 95% stability in mouse serum at day 5. PSMA-positive PC3 PIP cells demonstrated 89.6% ± 0.55% cell binding, 55.45% ± 0.96% internalization at 24 h, and a dissociation constant of 32.9 ± 3.9 nM, comparable to other reported [<sup>177</sup>Lu]Lu/[<sup>225</sup>Ac]Ac-PSMA-617 radiocomplexes. In contrast, no cellular uptake or internalization was observed in PSMA-negative PC3 flu cells. Clonogenic assay of [<sup>134</sup>Ce]Ce-PSMA-617 showed a significant dose-dependent reduction in cell proliferation (<i>P</i> = 0.002). PET imaging revealed high tumor-specific uptake at early time points (1 and 4 h), followed by a gradual decline from 24 to 72 h, with rapid clearance from normal tissues. These results were corroborated by ex vivo biodistribution studies. In vivo therapy with [<sup>134</sup>Ce]Ce-PSMA-617 in tumor-bearing mice demonstrated a significant increase in median survival compared with control animals (saline, 33 d; 37 MBq, 50 d; and 111 MBq, 80 d, end of the study). <b>Conclusion:</b> [<sup>134</sup>Ce]Ce-PSMA-617 exhibited excellent in&nbsp;vitro and in&nbsp;vivo characteristics, providing significant survival benefits in mice. Collectively, these findings suggest that [<sup>134</sup>Ce]Ce-PSMA-617 is an effective theranostic agent for PET imaging and AE therapy of prostate cancer.","journal":"Journal of Nuclear Medicine","year":2025,"id":544754,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9649,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1046353,"name":"Anju Wadhwa","orcid":"0009-0006-0826-8134","position":1,"is_corresponding":false},{"id":859469,"name":"Anil P. Bidkar","orcid":"0000-0003-1249-1081","position":2,"is_corresponding":false},{"id":1221619,"name":"Athira Raveendran","orcid":"0000-0002-4853-4330","position":3,"is_corresponding":false},{"id":555215,"name":"Luis Garcia","orcid":null,"position":4,"is_corresponding":false},{"id":336675,"name":"Nancy Greenland","orcid":"0000-0002-1783-1711","position":5,"is_corresponding":false},{"id":488328,"name":"David M. Wilson","orcid":"0000-0002-1095-046X","position":6,"is_corresponding":false},{"id":325839,"name":"Youngho Seo","orcid":"0000-0001-5908-6636","position":7,"is_corresponding":false},{"id":401718,"name":"Henry F. VanBrocklin","orcid":"0000-0003-2849-0841","position":8,"is_corresponding":false},{"id":272317,"name":"Robert R. Flavell","orcid":"0000-0002-8694-1199","position":9,"is_corresponding":false},{"id":1027131,"name":"Kondapa Naidu Bobba","orcid":"0000-0001-6304-2855","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-19T02:53:17.418915Z","pmid":"40506238","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":[]}