Development and Initial Evaluation of 64Cu-Labeled Disintegrin for PET Imaging of Prostate Cancer

1184 Objectives A novel recombinant disintegrin, vicrostatin (VCN), displays high binding affinity to a broad range of human integrins in substantial competitive biological advantage over other integrin-based antagonists. In this study, we synthesized a new 64Cu-labeled VCN probe and evaluated its imaging properties for prostate cancer in PC-3 tumor bearing mice. Methods Macrocyclic chelating agent 1,8-diamino-3,6,10,13,16,19-hexaazabicyclo[6.6.6]-eicosine (DiAmSar) was conjugated with PEG unit, and followed by a coupling with VCN. The precursor was then radiolabeled with positron emitter 64Cu (t1/2 = 12.7h) in ammonium acetate buffer to provide 64Cu-Sar-PET-VCN, which was subsequently subject to in vitro studies, small animal PET, and biodistribution studies. The PC-3 tumor targeting efficacy of 64Cu-Sar-PET-VCN was compared to a cyclic RGD peptide based PET probe (64Cu-Sar-RGD). Results 64Cu labeling was achieved in 75% decay-corrected yield with radiochemical purity of \u003e98%. The specific activity of 64Cu-Sar-PEG-VCN was estimated to be 37 MBq/nmol. MicroPET imaging results showed that 64Cu-Sar-PEG-VCN has preferential tumor uptake and good tumor retention in PC-3 tumor xenografts. As compared to 64Cu-Sar-RGD, 64Cu-Sar-PEG-VCN produces higher tumor-to-muscle (T/M) imaging contrast ratios at 2 h (4.66±0.34 vs. 2.88±0.46) and 24 h (4.98±0.80 vs. 3.22±0.30) post-injection (pi), and similar tumor-to-liver ratios at 2 h (0.43±0.09 vs. 0.37±0.04) and 24 h (0.57±0.13 vs. 0.52±0.07) pi. The biodistribution results were consistent with the quantitative analysis of microPET imaging, demonstrating good T/M ratio (2.73±0.36) of 64Cu-Sar-PEG-VCN at 48 h pi in PC-3 tumor xenografts. Conclusions 64Cu-Sar-PEG-VCN has the potential for in vivo imaging of prostate cancer with PET, which may provide a unique non-invasive method to quantitatively localize and characterize prostate cancer.