Targeting PSMA with a 64Cu-labeled phosphoramidate inhibitor for PET/CT imaging of variant PSMA-expressing xenografts in a mouse model of prostate cancer

497 Objectives CTT-97, an irreversible phosphoramidate inhibitor of PSMA, was conjugated to the CB-TE1K1P chelator for incorporation of 64Cu. The resulting PSMA-targeted PET agent, 64Cu-ABN-1, was evaluated for uptake in PSMA positive (PSMA+) cells of varying expression levels. This study assess the performance of 64Cu-ABN-1 in mouse models of prostate cancer. Methods 64Cu-ABN-1 was evaluated in vitro and in vivo in cell lines of varying levels of PSMA-expression: C4-2B, CWR22rv1, LNCaP and PSMA-negative PC3 cells. 64Cu-ABN-1 was evaluated by internalization and binding affinity assays. PET/CT imaging and biodistributions. Results The in vitro performance of 64Cu-ABN-1 demonstrated selective uptake in PSMA positive cells with approximately 80% internalization at 4 h for each PSMA+ cell lines. The uptake was correlated to PSMA expression levels. Imaging indicated significant tumor uptake with rapid non-target clearance through the kidneys. The PET/CT images for LNCaPs had the greatest uptake of 64Cu-ABN-1 (Figure 1). The LNCaPs were further evaluated in biodistribution experiments confirming the selective uptake in PSMA positive tumors with tumor:muscle and tumor: blood ratios (32 for both at 24 h). Conclusions 64Cu-ABN-1 demonstrated selective uptake in PSMA+ cells and tumors correlated to the level of PSMA expression. The ability of 64Cu-ABN-1 to selectively image variant PSMA-expressing xenografts demonstrates that the agent is capable of monitoring levels of PSMA-expression, and can be translated to the clinic as a non-invasive method to follow the progression of prostate cancer. These data, are encouraging, and we believe that optimization of the PSMA-targeted scaffold will enhance tumor uptake even further to provide an optimal agent for monitoring prostate cancer progression. Research Support University of Pittsburgh Medical Center Start Up