Title: Early detection of rheumatoid arthritis in rats and humans with 99mTc-3PRGD2 scintigraphy: imaging synovial neoangiogenesis
Abstract: // Yu Wu 1,2,* , Guojian Zhang 1,* , Xiangcheng Wang 1 , Zhenfang Zhao 1 , Tao Wang 1 , Xuemei Wang 1 and Xiao-Feng Li 3,4 1 Department of Nuclear Medicine, Inner Mongolia Medical University Affiliated Hospital, Hohhot, Inner Mongolia, China 2 Department of Nuclear Medicine, Inner Mongolia Medical University Affiliated People's Hospital, Hohhot, Inner Mongolia, China 3 PET/CT/MRI Center, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China 4 Department of Radiology, University of Louisville, Louisville KY, USA * These authors have contributed eqally to this work Correspondence to: Xuemei Wang, email: // Xiao-Feng Li, email: // Keywords : rheumatoid arthritis; synovial neoangiogenesis; 99mTc-3PRGD2; 99mTc-MDP; scintigraphy Received : July 06, 2016 Accepted : December 08, 2016 Published : December 15, 2016 Abstract Objectives: To validate 99m Tc-labeled arginylglycylaspartic acid ( 99m Tc-3PRGD2) scintigraphy as a means to image synovial neoangiogenesis in joints afflicted by rheumatoid arthritis and to investigate its potential in the early detection and management of rheumatoid arthritis. Methods: Rheumatoid arthritis and osteoarthritis were generated in Sprague Dawley rats by type II collagen immunization and papain injection, respectively. Rats were imaged with 99m Tc-3PRGD2 and 99m Tc- methyl diphosphonate ( 99m Tc MDP). X-ray images were also obtained and assessed by a radiologist. Immunohistochemistry of α v β 3 and CD31confirmed the onset of synovial neoangiogenesis. The effect of bevacizumab on rheumatoid arthritis was followed with 99m Tc-3PRGD2 scintigraphy. A patient with rheumatoid arthritis and a healthy volunteer were scanned with 99m Tc-3PRGD2. Results: Two weeks after immunization, a significant increase in 99m Tc-3PRGD2 was observed in the joints of the rheumatoid arthritis model though uptake in osteoarthritis model and untreated controls was low. 99m Tc-MDP whole body scans failed to distinguish early rheumatoid arthritis joints from healthy controls. The expression of α v β 3 and CD31was significantly higher in the joints of rheumatoid arthritis rats compared to normal controls. In serial 99m Tc-3PRGD2 scintigraphy studies, 99m Tc-3PRGD2 uptake increased in parallel with disease progression. Bevacizumab anti-angiogenetic therapy both improved the symptoms of the rheumatoid arthritis rats and significantly decreased 99m Tc-3PRGD2 uptake. Significantly higher 99m Tc-3PRGD2 accumulation was also observed in rheumatoid arthritis joints in the patient. Conclusions: Our findings indicate that 99m Tc-3PRGD2 scintigraphy could detect early rheumatoid arthritis by imaging the associated synovial neoangiogenesis, and may be useful in disease management.