Synthesis and evaluation of [ 64 Cu]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 (Cu-64), to evaluate the metabolism, biodistribution, and potential of [Cu-64] PSMA-617 for PET imaging of prostate cancer. [Cu-64] PSMA-617 was synthesized by heating PSMA- 617 with [Cu-64] CuCl2 in buffer solution at 90 degrees 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 Cu-64 for PSMA-617 yielded [Cu-64] PSMA-617 with >99% radiochemical purity. In vitro cellular uptake experiments demonstrated the specificity of [Cu-64] PSMA-617 for PSMA- positive LNCaP cells. Biodistribution observations of normal mice revealed high uptake of radioactivity in the kidney and liver. PET with [Cu-64] PSMA- 617 visualized tumor areas implanted by PSMA-positive LNCaP cells in the mice. Two hours after the injection of [Cu-64] PSMA-617 into mice, a radiolabeled metabolite was observed in the blood, liver, urine, and LNCaP tumor tissues. [Cu-64] 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 Cu-64 or Cu-67-labeled PSMA ligands for imaging and radiotherapy.