title: Evaluation of 188Re-MAG2-RGD-bombesin for potential prostate cancer therapy.
abstract: Glu-RGD-bombesin (RGD-BBN) is a heterodimeric peptide that contains motifs recognizing both integrin α(v)β(3) and gastrin releasing peptide receptor (GRPR). We evaluated here (188)Re (t(1/2)=16.9 h) labeled RGD-BBN as a potential agent for radionuclide therapy of prostate cancer. RGD-BBN was conjugated with S-benzoylmercaptoacetylglycylglycyl (MAG(2)), and then labeled with (99m)Tc or (188)Re, respectively. The dual-receptor binding affinity of MAG(2)-RGD-BBN was investigated by a radioligand competition binding assay. Biodistribution study of (188)Re-MAG(2)-RGD-BBN was carried out in normal BALB/c mice and PC-3 human prostate tumor-bearing nude mice. Gamma imaging studies were performed in PC-3 tumor-bearing nude mice. Biodistribution in normal mice showed that both (99m)Tc and (188)Re-labeled MAG(2)-RGD-BBN possessed high pancreas uptake due to the high GRPR expression of this organ. Gamma imaging with both (99m)Tc and (188)Re-labeled RGD-BBN in PC-3 tumor-bearing nude mice demonstrated high tumor uptake. The PC-3 tumors were clearly visible at 1 postinjection, with high contrast to the contralateral background. The use of chelator MAG(2) enables successful and high-yield (99m)Tc and (188)Re radiolabeling of RGD-BBN with favorable tumor targeting specificity. Further optimization may allow potential clinical application of (188)Re-MAG(2)-RGD-BBN for tumor-targeted radionuclide therapy.
authors.affiliation: Medical Isotopes Research Center, Peking University, Beijing 100191, China.
authors.forename: Liyang
authors.initials: L
authors.lastname: Cui
authors.forename: Zhaofei
authors.initials: Z
authors.lastname: Liu
authors.forename: Xiaona
authors.initials: X
authors.lastname: Jin
authors.forename: Bing
authors.initials: B
authors.lastname: Jia
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
mesh_terms: D000818:Animals; D001839:Bombesin / Q000378:metabolism*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D004151:Dipeptides / Q000378:metabolism* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D051379:Mice; D009842:Oligopeptides / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy*; D011854:Radiochemistry; D011868:Radioisotopes / Q000627:therapeutic use*; D011874:Radiometry; D011877:Radionuclide Imaging; D018000:Receptors, Peptide / Q000378:metabolism; D012211:Rhenium / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D004151:Dipeptides; D009842:Oligopeptides; D011868:Radioisotopes; D018000:Receptors, Peptide; C557099:S-benzoylmercaptoacetylglycylglycyl; D012211:Rhenium; C047981:arginyl-glycyl-aspartic acid; D001839:Bombesin