Synthesis and evaluation of [⁶⁴Cu]PSMA-617 targeted for prostate-specific membrane antigen in prostate cancer

We radiolabeled a ligand, PSMA-617, of prostate-specific membrane antigen (PSMA) with copper-64 (⁶⁴Cu), to evaluate the metabolism, biodistribution, and potential of [⁶⁴Cu]PSMA-617 for PET imaging of prostate cancer. [⁶⁴Cu]PSMA-617 was synthesized by heating PSMA-617 with [⁶⁴Cu]CuCl₂ in buffer solution at 90°C for 5 min. In vitro uptake was determined in two cell lines of prostate cancer. In vivo regional distributions were determined in normal and tumor-bearing mice. High radiolabeling efficiency of ⁶⁴Cu for PSMA-617 yielded [⁶⁴Cu]PSMA-617 with >99% radiochemical purity. In vitro cellular uptake experiments demonstrated the specificity of [⁶⁴Cu]PSMA-617 for PSMA-positive LNCaP cells. Biodistribution observations of normal mice revealed high uptake of radioactivity in the kidney and liver. PET with [⁶⁴Cu]PSMA-617 visualized tumor areas implanted by PSMA-positive LNCaP cells in the mice. Two hours after the injection of [⁶⁴Cu]PSMA-617 into mice, a radiolabeled metabolite was observed in the blood, liver, urine, and LNCaP tumor tissues. [⁶⁴Cu]PSMA-617 was easily synthesized, and exhibited a favorable biodistribution in PSMA-positive tumors. Although this radioligand shows slow clearance for kidney and high liver uptake, change of its chelator moiety and easy radiolabeling may enable development of new ⁶⁴Cu or ⁶⁷Cu-labeled PSMA ligands for imaging and radiotherapy.