Date: Tuesday, October 23, 2018
Session Title: Imaging of Rheumatic Diseases Poster III: Other Modalities
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Activated macrophages are a critical component of the inflammatory etiology of RA. It is well established that these macrophages perpetuate joint inflammation and destruction through the release of pro-inflammatory cytokines and chemokines, and that a preponderance of these macrophages express the CD206 marker. Tc 99m tilmanocept selectively targets CD206 with high affinity (KD = 2.76 x 10-11). In this report, we describe planar and SPECT/CT imaging findings from a clinical study examining the safety and efficacy of intravenously (IV) administered Tc 99m tilmanocept in subjects with active RA and healthy controls (HC). These results provide significant insight into the longitudinal quantitative immunodiagnostic potential of tilmanocept in the rheumatological space.
Methods: Subjects with active RA were required to have a clinical diagnosis of moderate to severe RA in accordance with the 2010 ACR/EULAR criteria and a DAS28 score of ≥ 3.2. HC subjects were required to be deemed clinically free of any inflammatory disease. The images in this report were obtained at 60 ± 15 minutes post-IV administration of the maximum study dose of 400 µg tilmanocept radiolabeled with 10 mCi of Tc 99m. Subjects with active RA underwent static planar imaging of the whole body and bilateral hands followed by additional SPECT/CT in areas of increased radiopharmaceutical uptake. HCs underwent static planar imaging of the whole body and bilateral hands only.
Results: Tc 99m tilmanocept was well-tolerated and no drug-related adverse events were observed. Static planar images of joints in active RA subjects demonstrated significant Tc 99m tilmanocept localization to disease-involved joints of the shoulders, knees, hands, and feet. These findings were further interrogated on SPECT/CT, which revealed greater anatomical delineation of localization specifically to the joint space. Whole body and joint-specific static planar imaging in healthy control subjects failed to demonstrate joint-specific localization.
Conclusion: There are currently no FDA-approved functional imaging modalities for the assessment of macrophage-driven arthropathy in patients with clinically diagnosed active RA. The ability to detect synovial macrophage activity from planar and SPECT/CT imaging makes Tc 99m tilmanocept a valuable immunodiagnostic agent for the evaluation of joint-specific inflammation, characterization of joint-level pathobiology, and individualization of treatment. Further studies examining the concordance of tilmanocept uptake with CD206-positive synovial macrophages over time may provide valuable, clinically significant insight into the ability to quantitatively monitor treatment response.
To cite this abstract in AMA style:Kardan A, Kissling A, Abbruzzese B, Ismail A, Hershey R, Hartings C, Ralph D, Gierach I, Blue M, Bailey H, Gablemann C, Repp K, Cope F. Technetium Tc 99m Tilmanocept: A Targeted Immunodiagnostic Radiopharmaceutical for the Assessment of Synovial Macrophage Activity in Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/technetium-tc-99m-tilmanocept-a-targeted-immunodiagnostic-radiopharmaceutical-for-the-assessment-of-synovial-macrophage-activity-in-rheumatoid-arthritis/. Accessed March 21, 2023.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/technetium-tc-99m-tilmanocept-a-targeted-immunodiagnostic-radiopharmaceutical-for-the-assessment-of-synovial-macrophage-activity-in-rheumatoid-arthritis/