title: 177Lu-labeled RGD-BBN heterodimeric peptide for targeting prostate carcinoma.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Miao
authors.forename: Hongguang
authors.initials: H
authors.lastname: Liu
authors.forename: Gang
authors.initials: G
authors.lastname: Ren
authors.forename: Ande
authors.initials: A
authors.lastname: Bao
authors.forename: Cathy S
authors.initials: CS
authors.lastname: Cutler
authors.forename: Hongcheng
authors.initials: H
authors.lastname: Shi
authors.forename: Zhen
authors.initials: Z
authors.lastname: Cheng
mesh_terms: D000818:Animals; D001372:Aza Compounds / Q000737:chemistry; D001839:Bombesin / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D019281:Dimerization; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D006801:Humans; D008187:Lutetium / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D058990:Molecular Targeted Therapy / Q000379:methods*; D009842:Oligopeptides / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D011829:Radiation Dosage; D011854:Radiochemistry; D011868:Radioisotopes / Q000627:therapeutic use
chemical_list: C578439:1,4,7,10-tetraazacyclododecane-1,4,7,10-tetracetic acid; D001372:Aza Compounds; D006573:Heterocyclic Compounds, 1-Ring; D009842:Oligopeptides; D011868:Radioisotopes; D008187:Lutetium; C047981:arginyl-glycyl-aspartic acid; D001839:Bombesin