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Imaging Cell Death with Radiolabeled Annexin V in an Experimental Model of Rheumatoid Arthritis

¹ Division of Nuclear Medicine, Department of Radiology, Stanford University, Stanford, California
² Department of Microbiology and Immunology, MCP Hahnemann University, Philadelphia, Pennsylvania
³ Department of Laboratory Medicine, University of Washington, Seattle, Washington
⁴ Department of Pathology, Stanford University, Stanford, California
⁵ Division of Nuclear Medicine, Department of Radiology, Memorial Sloan-Kettering Hospital, New York, New York
⁶ Division of Pediatric Radiology, Department of Radiology, Lucile Salter Packard Children’s Hospital, Stanford, California

Rheumatoid arthritis is associated with chronic synovial inflammation due to the abnormal accumulation of macrophages and autoreactive T lymphocytes in joints. The autoreactive cells cause an inflammatory proapoptotic response to self-antigens resulting in eventual bone, cartilage, and soft-tissue loss and destruction. The goal of our study was to determine the timing and intensity of apoptosis in joints using ^99mTc-labeled annexin V, an in vivo marker of apoptosis, in a murine model of immune arthritis. Methods: We used ^99mTc-annexin V and autoradiography to study the extent and severity of apoptosis in the front and rear paws of DBA/1 mice with type II collagen-induced rheumatoid arthritis. Results: Compared with control values (n = 10), there was a significant (P < 0.002) nearly 3-fold increase in uptake of ^99mTc-annexin V in the front foot pads, rear toes, rear foot pads, and heels at the time of maximal extremity swelling as determined by serial caliper measurements at 4 wk after inoculation with type II bovine collagen (n = 9). The front toes had a 5- to 6-fold increase in uptake compared with control values (P < 0.001). Histologic analysis revealed only scattered rare lymphocytes in the periarticular soft tissues, without joint destruction. Dual autoradiography with ¹²⁵I-bovine serum albumin as a control showed that ^99mTc-annexin V localization was specific. Treatment with methylprednisolone for 1 wk (n = 8) at 4 wk after immunization with type II collagen decreased ^99mTc-annexin V uptake by 3- to 6-fold compared with control values (P < 0.002). Conclusion: ^99mTc-annexin V can detect collagen-induced immune arthritis and its response to steroid therapy before joint destruction.

Key Words: annexin V • rheumatoid arthritis • apoptosis • radionuclide

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