[(131)I labeling and bioactivity evaluation of a novel RGD dimer targeted to integrin αvβ3 receptor]

To study the (131)I labeling, tumor targeting property, biodistrubution and imaging of a novel disulfide bridged Arg-Gly-Asp (RGD) peptide dimer and investigate its possibility for tumor angiogenesis imaging.

A disulfide bridged cRGD peptide dimer [c(RGD)2] was designed according to the published RESULTS of structure-activity relationship study of c(RGDfV) and modified with hydrophilic amino acid. The affinity of the peptide to αvβ3 receptor was determined by binding assay. The peptide was labeled with (131)I by ChT method. The stability and lg n-octanol-water partition coefficient of the labeled peptide were tested. The biodistribution, inhibition with unlabeled peptide and imaging were performed by injecting the labeled peptide into the mice bearing meloma B16.

The (131)I labeling efficiency and radiochemical purity were (76.35 ± 2.33)% and (95.20 ± 3.25)%, respectively. Ka was (0.137 ± 0.057) × 10(9) /mol/L, and lgPo(ctanol/water) was-1.628. The tumor uptake of the labeled peptide at 1 h, 3 h, 5 h and 24 h were (0.67 ± 0.13)%ID/g, (0.42 ± 0.08)%ID/g, (0.51± 0.11)%ID/g and (0.18 ± 0.02)%ID/g, respectively. The tumor clearance was low, so the T/NT increased with time. The T/M and T/B were 4.42 ± 1.70 and 2.27 ± 0.45, respectively, 24 h post-injection. The hepatic uptake of the labeled peptide was low. The tumor-to-liver ratio was 2.10 ± 0.60 at 1 h post-injection, coinjection of c(RGD)2 with (131)I-c(RGD)2 resulted in a significant decrease in tumor uptake. In total body images, only kidneys were distinctive whereas tumor was clear in chest images 3 h post-injection.

c(RGD)2 can be successfully labeled with (131)I by ChT method. The labeled peptide can be specifically combined with tumor, which suggests its possibility in tumor angiogenesis imaging. Its low liver uptake provides an advantage for tumor imaging.