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

We recently developed I-125- and At-211-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 alpha(v)beta(3) integrin. We synthesized an iodine-introduced dimer RGD peptide, E[c(RGDfK)] (6), and an I-125/131-labeled dimer RGD peptide, E[c(RGDfK)]{[I-125/131]c[RGDf(4-I)K]} ([I-125/131]6), and evaluated them as a preliminary step to the synthesis of an At-211-labeled dimer RGD peptide. The affinity of 6 for alpha(v)beta(3) integrin was higher than that of a monomer RGD peptide. In the biodistribution experiment at 4 h postinjection, the accumulation of [I-125]6 (4.12 & PLUSMN; 0.42% ID/g) in the tumor was significantly increased compared with that of I-125-labeled monomer RGD peptide (2.93 & PLUSMN; 0.08% ID/g). Moreover, the accumulation of [I-125]6 in the tumor was greatly inhibited by co-injection of an excess RGD peptide. However, a single injection of [I-131]6 (11.1 MBq) did not inhibit tumor growth in tumor-bearing mice. We expect that the labeling method for targeted alpha therapy with At-211 using a dimer RGD peptide could prove useful in future clinical applications.

Automated summary

Novel radiolabeling method was developed for I-125 and At-211-labeled RGD peptides, showing high accumulation in tumor tissues and similar biodistribution. Dimer RGD peptides demonstrated improved affinity with alpha(v)beta(3) integrin, leading to higher accumulation in tumor tissues. Furthermore, experiments showed significantly increased accumulation of I-125-labeled dimer RGD peptide in tumors compared to monomer RGD peptide.