Introduction: Radiolabeled Arg-Gly-Asp (RGD) and bombesin (BBN) heterodimers have been investigated for dual targeting of tumor integrin αvβ3 receptors and gastrin-releasing peptide receptors. The goal of this study was to evaluate the potential use of a 177Lu-labeled RGD-BBN heterodimer for targeted prostate cancer therapy.
Materials and methods: A 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-conjugated RGD-BBN peptide (DO3A-RGD-BBN) was radiolabeled with 177Lu and purified by high-performance liquid chromatography. The in-vivo biodistribution study of 177Lu-DO3A-RGD-BBN was carried out in mice bearing human prostate cancer PC3 xenografts. The receptor-targeting specificity of the radiolabeled peptide was assayed by injecting the tracer with the unlabeled RGD-BBN peptide. Radiation absorbed doses in adult male patients, based on biodistribution data from mice, were also calculated.
Results: DO3A-RGD-BBN peptides were successfully labeled with 177Lu, and high radiochemical purity (>95%) could be achieved after high-performance liquid chromatography purification. 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 48 h, respectively. With rapid clearance from normal tissues, the radiolabeled probe displayed high tumor-to-blood and tumor-to-muscle ratios. On calculating the radiation absorbed doses for 177Lu-DO3A-RGD-BBN, we found that the prostate tumor and the pancreas were the organs receiving the highest radiation absorbed doses.
Conclusion: Dual integrin αvβ3 and GPRP-targeted agent 177Lu-DO3A-RGD-BBN shows excellent prostate cancer-targeting ability, and it is worthy of further evaluation for prostate cancer-targeted therapy.
aDepartment of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
bMolecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Canary Center at Stanford for Cancer Early Detection, Stanford Cancer Institute, Stanford University, Stanford, California
cDepartment of Radiation Oncology, Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, Ohio
dResearch Reactor Center (MURR), Radiopharmaceutical Sciences Institute, Nuclear Engineering and Sciences Institute, University of Missouri, Columbia, Missouri, USA
Correspondence to Zhen Cheng, PhD, Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Canary Center at Stanford for Cancer Early Detection, Stanford Cancer Institute, Stanford University, 1201 Welch Road, Lucas Expansion, P095, Stanford, CA 94305, USA Tel: +1 650 723 7866; fax: +1 650 736 7925; e-mail: firstname.lastname@example.org
Received November 14, 2012
Accepted May 1, 2013