Direct in vivo evidence of activated macrophages in human osteoarthritis V.B. Kraus, G. McDaniel, J.L. Huebner, T.V. Stabler, C.F. Pieper, S.W. Shipes,

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Presentation transcript:

Direct in vivo evidence of activated macrophages in human osteoarthritis V.B. Kraus, G. McDaniel, J.L. Huebner, T.V. Stabler, C.F. Pieper, S.W. Shipes, N.A. Petry, P.S. Low, J. Shen, T.A. McNearney, P. Mitchell Osteoarthritis and Cartilage Volume 24, Issue 9, Pages 1613-1621 (September 2016) DOI: 10.1016/j.joca.2016.04.010 Copyright © 2016 Osteoarthritis Research Society International Terms and Conditions

Fig. 1 Structure of the EC20 imaging reagent. Folate, the targeting moiety, is shown on the left; the chelating agent to which 99mTc is conjugated, is shown on the right. Osteoarthritis and Cartilage 2016 24, 1613-1621DOI: (10.1016/j.joca.2016.04.010) Copyright © 2016 Osteoarthritis Research Society International Terms and Conditions

Fig. 2 Consort Flow Diagram. Flow of participants through each stage of the observational study. Osteoarthritis and Cartilage 2016 24, 1613-1621DOI: (10.1016/j.joca.2016.04.010) Copyright © 2016 Osteoarthritis Research Society International Terms and Conditions

Fig. 3 Representative patterns and intensity of Etarfolatide uptake in each of the 50 knees. Representative images (top row) of Etarfolatide uptake in the: A) joint ‘capsule’ (showing capsular and/or underlying synovial uptake, indicated in coronal view by arrowhead); B) ‘synovium’ (showing uptake by proliferative synovium in the posterior synovial recess, indicated in coronal and sagittal views by arrow); C) ‘synovium’ and joint ‘capsule’ (indicated in sagittal view by arrow and arrowhead, respectively); and D) bone (indicated in coronal view by asterisk). Heat map graphic (bottom) representing the uptake intensity for each knee as quantified for three regions: joint ‘capsule’, ‘synovium’ and subchondral bone; the maximum score for each joint region was 6, 6 and 5, respectively. Osteoarthritis and Cartilage 2016 24, 1613-1621DOI: (10.1016/j.joca.2016.04.010) Copyright © 2016 Osteoarthritis Research Society International Terms and Conditions

Fig. 4 Knee radiographs, Etarfolatide scans and synovial fluid cell immunohistochemistry for knees of two study participants. In both participants, the left knee was the index knee. The panels on the left correspond to one participant and on the right to a second participant). Top: Bilateral anteroposterior knee radiographs show OA bilaterally with more severe disease of the left knees for each participant; total OA severity scores (joint space narrowing plus osteophyte) were 5, 9, 3 and 11 for right and left knees of participants 24 and 25 respectively. Corresponding pain scores were 1, 3, 1 and 3 respectively. Middle: The total Etarfolatide knee scores were 3, 5, 0 and 9 respectively (the second row shows SPECT images and the third row shows matched fused SPECT-CT images of the knee; coronal and transaxial images include both right and left knees, and the sagittal images include the index left knees of each participant. Synovial fluid cytospins were stained for iNOS, FR-β and TGF-β. Merged images demonstrate co-expression of FR-β (identifying the cells as activated macrophages), an M1 macrophage marker (iNOS) and an M2 macrophage marker (TGF-β). R = right knee; L = left knee. Osteoarthritis and Cartilage 2016 24, 1613-1621DOI: (10.1016/j.joca.2016.04.010) Copyright © 2016 Osteoarthritis Research Society International Terms and Conditions