Evaluation of Ce/La-PSMA-617 for PET Imaging and Auger Electron Therapy of Prostate Cancer.

The Ce/La radionuclide pair has been proposed as a PET imaging surrogate for targeted α-radiotherapeutics. Ce decays to 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 Ce/La a promising theranostic pair for prostate cancer. In this work, we investigated the potential of Ce for AE capture therapy using prostate-specific membrane antigen (PSMA)-617 for targeted radionuclide delivery. Radiolabeling of [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 vivo single-dose-treatment study was performed using 37- and 111-MBq doses in nude mice with PC3 PIP tumor xenografts. PSMA-617 was successfully radiolabeled with Ce/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 [Lu]Lu/[Ac]Ac-PSMA-617 radiocomplexes. In contrast, no cellular uptake or internalization was observed in PSMA-negative PC3 flu cells. Clonogenic assay of [Ce]Ce-PSMA-617 showed a significant dose-dependent reduction in cell proliferation ( = 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 [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). [Ce]Ce-PSMA-617 exhibited excellent in vitro and in vivo characteristics, providing significant survival benefits in mice. Collectively, these findings suggest that [Ce]Ce-PSMA-617 is an effective theranostic agent for PET imaging and AE therapy of prostate cancer.