Evaluation of synovial angiogenesis in patients with rheumatoid arthritis using 68Ga-PRGD2 PET/CT: a prospective proof-of-concept cohort study

BACKGROUND The study aimed to evaluate the use of positron emission tomography/computed tomography (PET/CT) with (68)Ga-PRGD2 as the tracer for imaging of synovial angiogenesis in patients with rheumatoid arthritis (RA). METHODS Twenty untreated active patients with RA underwent (68)Ga-PRGD2 PET/CT and (18)F-FDG PET/CT before treatment; two patients with osteoarthritis served as controls. Among the 20 patients with RA, 12 repeated the evaluations after 3-month treatment. The image findings were correlated with core variables of disease activity, including the clinical disease activity index (cDAI). RESULTS Our findings demonstrated that (68)Ga-PRGD2 specifically accumulated in the synovia with active inflammation rich in neovasculature with high-level αvβ3-integrin expression, but not in the (18)F-FDG-avid inflammatory lymph nodes. In patients with intense (18)F-FDG uptake in muscles caused by arthritic pain, we observed that (68)Ga-PRGD2 PET/CT was better able to evaluate disease severity than (18)F-FDG PET/CT. Both (68)Ga-PRGD2 accumulation and (18)F-FDG uptake changed in response to therapeutic intervention, whereas the changes of (68)Ga-PRGD2, not (18)F-FDG, significantly correlated with clinical measures of changes in the form of cDAI. CONCLUSIONS This is the first integrin imaging study conducted in patients with RA that preliminarily indicates the effectiveness of the novel method for evaluating synovial angiogenesis. CLINICAL TRIAL REGISTRATION This study has been registered online at NIH ClinicalTrial.gov (NCT01940926).