Evaluation of Re-188-MAG(2)-RGD-bombesin for potential prostate cancer therapy

Glu-RGD-bombesin (RGD-BBN) is a heterodimeric peptide that contains motifs recognizing both integrin alpha(v)beta(3) and gastrin releasing peptide receptor (GRPR). We evaluated here Re-188 (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 Tc-99m or Re-188, respectively. The dual-receptor binding affinity of MAG(2)-RGD-BBN was investigated by a radioligand competition binding assay. Biodistributions study of Re-188-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 Tc-99m and Re-188-labeled MAG(2)-RGD-BBN possessed high pancreas uptake due to the high GRPR expression of this organ. Gamma imaging with both Tc-99m and Re-188-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 Tc-99m and Re-188 radiolabeling of RGD-BBN with favorable tumor targeting specificity. Further optimization may allow potential clinical application of Re-188-MAG(2)-RGD-BBN for tumor-targeted radionuclide therapy. (C) 2013 Elsevier Inc. All rights reserved.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000314625300005&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Radiology, Nuclear Medicine & Medical ImagingSCI(E)PubMed1ARTICLE2182-1894