Evaluation of 188Re-MAG2-RGD-bombesin for potential prostate cancer therapy.

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.