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 Lu-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 Lu and purified by high-performance liquid chromatography. The in-vivo biodistribution study of Lu-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 Lu, and high radiochemical purity (>95%) could be achieved after high-performance liquid chromatography purification. In human PC3 xenograft-bearing mice, the tumor accumulation of Lu-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 Lu-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 Lu-DO3A-RGD-BBN shows excellent prostate cancer-targeting ability, and it is worthy of further evaluation for prostate cancer-targeted therapy.
Written by:
Jiang L, Miao Z, Liu H, Ren G, Bao A, Cutler CS, Shi H, Cheng Z. Are you the author?
Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai, China; 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, Stanford, California; Department of Radiation Oncology, Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, Ohio; Research Reactor Center (MURR), Radiopharmaceutical Sciences Institute, Nuclear Engineering and Sciences Institute, University of Missouri, Columbia, Missouri, USA.
Reference: Nucl Med Commun. 2013 May 23. Epub ahead of print.
doi: 10.1097/MNM.0b013e328362d2b6
PubMed Abstract
PMID: 23708872
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