Study of novel molecular probe 99mTc-3PRGD2 in the diagnosis of rheumatoid arthritis

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Abstract

Introduction

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 99mTc-radiolabeled, 99mTc(HYNIC-3PRGD2)(tricine) (TPPTS) (99mTc-3PRGD2 in short) in the diagnosis of RA.

Materials and methods

99mTc-3PRGD2 was synthesized using an HYNIC-3PRGD2 lyophilized kit with 99mTcO4− 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 99mTc-3PRGD2 was compared. Immunohistochemical staining was used to test the expression of integrin αvβ3 in the ankle tissue, analyzing the correlation between uptake of 99mTc-3PRGD2 and receptor expression.

Results

Planar imaging of arthritic ankles became visible at 30 min postinjection of 99mTc-3PRGD2 and was still clear at 6 h postinjection. The AI score increased, along with the uptake of 99mTc-3PRGD2. A biodistribution study showed that 99mTc-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 99mTc-3PRGD2 and the integrin αvβ3 expression levels in immunohistochemical study.

Conclusion

99mTc-3PRGD2 is a promising radiotracer for the diagnosis of RA.

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