Evaluation of synovial angiogenesis in patients with rheumatoid arthritis using (68)Ga-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 α(v)β(3)-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).