Synthesis and Evaluation of a Dimeric RGD Peptide as a Preliminary Study for Radiotheranostics with Radiohalogens.

We recently developed I- and At-labeled monomer RGD peptides using a novel radiolabeling method. Both labeled peptides showed high accumulation in the tumor and exhibited similar biodistribution, demonstrating their usefulness for radiotheranostics. This study applied the labeling method to a dimer RGD peptide with the aim of gaining higher accumulation in tumor tissues based on improved affinity with αβ integrin. We synthesized an iodine-introduced dimer RGD peptide, E[c(RGDfK)] (), and an I-labeled dimer RGD peptide, E[c(RGDfK)]{[I]c[RGDf(4-I)K]} ([I]), and evaluated them as a preliminary step to the synthesis of an At-labeled dimer RGD peptide. The affinity of for αβ integrin was higher than that of a monomer RGD peptide. In the biodistribution experiment at 4 h postinjection, the accumulation of [I] (4.12 ± 0.42% ID/g) in the tumor was significantly increased compared with that of I-labeled monomer RGD peptide (2.93 ± 0.08% ID/g). Moreover, the accumulation of [I] in the tumor was greatly inhibited by co-injection of an excess RGD peptide. However, a single injection of [I] (11.1 MBq) did not inhibit tumor growth in tumor-bearing mice. We expect that the labeling method for targeted alpha therapy with At using a dimer RGD peptide could prove useful in future clinical applications.