177Lu-labeled RGD-BBN heterodimeric peptide for prostate carcinoma targeting

1316 Objectives Radiolabeled Arg-Gly-Asp(RGD) and bombesin(BBN) heterodimers have been investigated for dual targeting of tumor integrin αvβ3 and gastrin-releasing peptide receptors(GRPR).The goal of this study was to evaluate the potential use of a 177Lu labeled RGD-BBN heterodimer for targeted prostate cancer therapy. Methods A 1,4,7,10-tetraazacyclododecane-N,N’,N’’N’’’-tetraacetic acid(DOTA) conjugated RGD-BBN peptide was radiolabeled with 177Lu and purified by high performance liquid chromatography(HPLC).The in vivo biodistribution study of 177Lu-DO3A-RGD-BBN was performed in mice bearing human prostate cancer PC3 xenografts. The receptor targeting specificity of the radiolabeled peptide was assayed by coinjecting of the tracer with the unlabeled RGD-BBN peptide. Radiation absorbed doses in human male adults were also calculated based on the mouse biodistribution data. Results DO3A-RGD-BBN peptides were successfully labeled with 177Lu and high radiochemical purity(>95%) could be achieved.In human PC3 xenograft-bearing mice, the tumor accumulation of 177Lu-DO3A-RGD-BBN was 5.88±1.12, 2.77±0.30,2.04±0.19 and 1.18±0.19%ID/g at 0.5, 2, 24 and 48h, respectively.With the rapid clearance from the normal tissues, the radiolabeled probe displayed high tumor to blood and tumor to muscle ratios.Calculation of radiation absorbed doses for 177Lu-DO3A-RGD-BBN suggested that prostate tumor and pancreas were organs receiving the highest radiation absorbed doses. Conclusions Dual integrin αvβ3 and GPRP targeted agent 177Lu-DO3A-RGD-BBN has emerged to be a promising for prostate cancer targeted therapy and imaging. Research Support DOD-PCRP-NIA PC094646 (to Z. Cheng), National Science Foundation for Scholars of China (Grant No. 81271608, 81101072, to H.C. Shi and L. Jiang, respectively). The production of 177Lu was supported by Department of Energy Grant 84900-001-10.