Imaging cell death with radiolabeled annexin V in an experimental model of rheumatoid arthritis.
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).


CONCLUSIONS
99mTc-annexin V can detect collagen-induced immune arthritis and its response to steroid therapy before joint destruction.
D000818:Animals; D017304:Annexin A5; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D017209:Apoptosis; D001169:Arthritis, Experimental / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000209:etiology; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000209:etiology; D003094:Collagen; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D051379:Mice; D008811:Mice, Inbred DBA; D011877:Radionuclide Imaging; D012711:Serum Albumin, Radio-Iodinated; D013667:Technetium
D017304:Annexin A5; D000893:Anti-Inflammatory Agents; D012711:Serum Albumin, Radio-Iodinated; D013667:Technetium; D003094:Collagen; D008775:Methylprednisolone