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The use of technetium tc 99m annexin V for in vivo imaging of apoptosis during cardiac allograft rejection
Ist Teil von
The Journal of thoracic and cardiovascular surgery, 1998-11, Vol.116 (5), p.844-853
Ort / Verlag
United States: Mosby, Inc
Erscheinungsjahr
1998
Quelle
MEDLINE
Beschreibungen/Notizen
Objective: Apoptosis, or programmed cell death, has been suggested as a mechanism of immunologic injury during cardiac allograft rejection. We 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
99mTc-annexin V imaging daily for 7 days. Region of interest analysis was used to quantify the uptake of
99mTc-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 rejecting allografts. Nuclear imaging revealed a significantly greater uptake of
99mTc-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 the histologic grade of acute rejection and uptake of
99mTc-annexin V was observed (
r
2 = 0.87). After treatment of rejection with cyclosporine, no apoptotic nuclei could be identified in allografts and uptake of
99mTc-annexin V decreased to baseline.
Conclusions: Apoptosis occurs during acute cardiac allograft rejection and disappears after treatment of rejection.
99mTc-annexin V can be used to detect and monitor cardiac allograft rejection. (J Thorac Cardiovasc Surg 1998;116:844-53)