⁶⁴Cu-PSMA-BCH-ZL PET imaging of prostate cancer patients and it’s potential application in peptide receptor- radionuclide guided surgery

Purpose: Here we synthesized a NOTA (1,4,7-triazacyclononane-triacetic acid) conjugated PSMA ligand named PSMA-BCH-ZL. ⁶⁴Cu was selected as a PET imaging radionuclide due to it long half decay time (T_1/2 = 12.7 h). ⁶⁴Cu-PSMA-BCH-ZL tracer were radiolabeled, pre-clinical and in-man studies were conducted to evaluate its potential as an imaging agent for PCa imaging and as a peptide receptor radionuclide guided surgery. Methods NOTA-conjugated ligand PSMA-BCH-ZL was prepared and radiolabeled with ⁶⁴CuCl₂. The in vitro and in vivo stability, partition coefficient, cell uptake in 22Rv1 and PC-3 cell lines were evaluated. Biodistribution and micro-PET imaging in mice bearing 22Rv1 and PC-3 at 11 h p.i. were performed. After approval by ethical committee, PET/CT scans on a patient with PCa (age 68, PSA 8.5 ng/mL) were performed at 1 h, 8 h, 24 h and 32 h post injection. Result ⁶⁴Cu-PSMA-BCH-ZL was prepared with high yield (>95%). The uptake in 22Rv1 and PC-3 were 5.71±0.16 and 1.79±0.20 IA%/10⁶ cells at 120 min. the uptake in 22Rv1 can be blocked to 3.44±0.13 IA%/10⁶ cells by excess ZJ-43. Micro-PET imaging in mouse bearing 22Rv1 and PC-3 showed 22Rv1 tumor was clearly visualized at 11 h p.i.. Biodistribution in normal mice showed ⁶⁴Cu-PSMA-BCH-ZL was concentrated in kidney (29.15±1.85 ID%/g at 0.5 h p.i.) and fast cleared out, the uptake in liver was maintained at 0.56-0.80 ID%/g from 0.5 h to 15 h. PET/CT images of a 68-year-old patient showed clearly the lesion at 1hours p.i. High contrast imaging can be found with the radio-tracers metabolism. The highest T/NT value found at 32h after injection. Conclusion Qualified ⁶⁴Cu-PSMA-BCH-ZL was prepared and it was demonstrated stable in vitro and hydrophilic. ⁶⁴Cu-PSMA-BCH-ZL was concentrated in PSMA expressing cells and tumor, indicating it was PSMA specific. PET/CT scans on a patient showed clearly lesion detection ability. More than that, ⁶⁴Cu-PSMA-BCH-ZL exhibits feasibility to be used for peptide receptor- radionuclide guided surgery.

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