The use of technetium Tc 99m annexin V for in vivo imaging of apoptosis during cardiac allograft rejection

Objective: Apoptosis, or programmed cell death, has been suggested as a mechanism of immunologic injury during cardiac allograft rejection. Wee tested the hypothesis that technetium Tc 99m annexin V: a novel radiopharmaceutical used to detect apoptosis, can be used to detect cardiac allograft rejection by nuclear imaging, Methods: Untreated ACI rats served as recipients of allogeneic PVG rat (n = 66) or syngeneic ACI rat (n = 30) cardiac grafts. Untreated recipient animals underwent Tc-99m-annexin V imaging daily for 7 days. Region of interest analysis was used to quantify the uptake of Tc-99m-annexin V. Immediately after imaging grafts were procured for histopathologic analysis and terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate-biotin nick-end labeling of apoptotic nuclei. One group was treated with 10 mg/kg/d cyclosporine (INN: ciclosporin) commencing on day 4 after transplantation (n = 6), Results: Untreated allografts showed histologic signs of rejection 4 days after transplantation, Apoptotic nuclei could be demonstrated in myocytes, endothelial cells, and graft-infiltrating cells of all I ejecting allografts, Nuclear imaging revealed a significantly greater uptake of Tc-99m-annexin V in rejecting allogeneic grafts than in syngeneic grafts on day 4 (P = .05), day 5 (P < .001), day 6 (P < .001) and day 7 (P = .013) after transplantation. A correlation between een the histologic grade of acute rejection and uptake of Tc-99m-annexin V was as observed (r(2) = 0.87), After treatment of rejection with cyclosporine! no apoptotic nuclei could be identified in allografts and uptake of Tc-99m-annexin V decreased to baseline. Conclusions: Apoptosis occurs during acute cardiac allograft rejection and disappears after treatment of rejection. Tc-99m-annexin V can be used to detect and monitor cardiac allograft rejection.