Angiogenesis in the synovial membrane plays an important role in the pathogenesis of rheumatoid arthritis (RA). Radiolabeled RGD (Arg-Gly-Asp) peptides can be used as a molecular probe in radionuclide imaging to assess angiogenesis noninvasively in vitro and investigate the process of RA to achieve the goal of early diagnosis and monitoring. The main objective of this study is to evaluate the value of RGD peptides conjugate with Tc-radiolabeled, Tc(HYNIC-3PRGD2)(tricine) (TPPTS) (Tc-3PRGD2 in short) in the diagnosis of RA.
Tc-3PRGD2 was synthesized using an HYNIC-3PRGD2 lyophilized kit with TcO4 labeling. Biodistribution and planar imaging studies were carried out in an RA rat model. The ankles were marked by arthritis index (AI) scores (from 0-3 score) according to the degree of ankle swelling and the ankle uptake of Tc-3PRGD2 was compared. Immunohistochemical staining was used to test the expression of integrin αvβ3 in the ankle tissue, analyzing the correlation between uptake of Tc-3PRGD2 and receptor expression.
Planar imaging of arthritic ankles became visible at 30 min postinjection of Tc-3PRGD2 and was still clear at 6 h postinjection. The AI score increased, along with the uptake of Tc-3PRGD2. A biodistribution study showed that Tc-3PRGD2 was excreted by the urinary system. The uptake by ankles with different AI scores was 0.64±0.07%ID/g (0 score), 1.10±0.07%ID/g (1 score), 1.30±0.04%ID/g (2 score), and 1.73±0.05%ID/g (3 score), respectively, at 1 h postinjection, suggesting that the ankle uptake increased with an increase in the AI score. There was a linear positive correlation relationship (r=0.852, P<0.05) between the ankle uptake of Tc-3PRGD2 and the integrin αvβ3 expression levels in immunohistochemical study.
Tc-3PRGD2 is a promising radiotracer for the diagnosis of RA.