LAUSR

Background In rheumatoid arthritis (RA), infiltrating macrophages play a critical role in the immunopathogenesis of the disease by generating pro-inflammatory cytokines and chemokines and by contributing directly to joint damage. Current imaging modalities do not directly assess activated macrophage-mediated disease processes in RA. Use of non-invasive imaging to detect macrophage infiltration of synovial joints may allow for more sensitive identification of synovitis and earlier recognition of RA, identify joints at risk for progressive inflammation and destruction, provide a better means of quantifying joint inflammation and disease activity, and measure or even predict response to macrophage-directed therapy. Tc 99 m tilmanocept is a synthetic radiopharmaceutical imaging agent that binds with high affinity to the mannose receptor (CD206) located on the cell surface of synovial macrophages. We investigated whether subcutaneous (SC) administration of tilmanocept labelled with Tc 99 m could specially image macrophage mediated inflammation in RA but not in healthy control (HC) subjects. Objectives To investigate whether subcutaneous (SC) administration of tilmanocept labelled with Tc 99 m could specially image macrophage mediated inflammation in RA but not in healthy control (HC) subjects. Methods Subjects received a SC injection of either 50 µg or 200 µg tilmanocept radiolabeled with 2mCi Tc99m in 0.4 mL. 18 subjects were enrolled as follows – Cohort 1: HC: 50 µg/2mCi; n=5; Cohort 2: HC: 200 µg/2mCi; n=4; Cohort 3: RA 50 µg/2mCi; n=4; Cohort 4: RA 200 µg/2mCi; n=5. Subjects were imaged with whole body planar scans at 2–3 hours and 4–6 hours post injection as well as separate 5 min planar images of both hands. If there were areas of increased localization, SPECT images were obtained. Results Tc 99 m tilmanocept localised most effectively at the 200 µg mass dose 2–3 hours post- administration in RA subjects (cohort 4). Localization was observed in 60% of the subjects in joints of the bilateral wrists, hands, and knees. No localization was observed in HCs receiving the same mass dose (cohort 2).Abstract AB0248 – Figure 1 Contrast of wrist and elbow of SC RA subject Conclusions Our findings represent a potential advance in the imaging of RA using a novel immunodiagnostic imaging strategy to specifically visualise macrophage-mediated elements of the RA disease process. This study demonstrates the potential for Tc 99 m tilmanocept to be used as an imaging tool for macrophage-mediated synovial inflammation in RA patients. This strategy can be used to identify patients at risk for activated macrophage-mediated joint damage, to quantify synovitis and disease activity, to provide further insight into immune-mediated mechanisms of RA, and to enable future targeted delivery of immunomodulatory therapeutics. Acknowledgements Navidea Biopharmaceuticals Russell Engleman Rheumatology Research Centre, University of California San Francisco Disclosure of Interest J. Graf Grant/research support from: Navidea Biopharmacueuticals, B. Abbruzzese: None declared, F. Cope: None declared, S. Behr: None declared, J. Sanders: None declared, A. Kissling: None declared, D. Ralph: None declared, J. Shuping: None declared, M. Blue: None declared, C. Hartings: None declared, R. Hershey: None declared, H. Bailey: None declared, A. spaulding: None declared, M. haynam: None declared, A. Ismail: None declared