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

• Published in: The Journal of thoracic and cardiovascular surgery Vol. 116; no. 5; pp. 844 - 853
• Main Authors: Vriens, Patrick W., Blankenberg, Francis G., Stoot a, Jan H., Ohtsuki, Katsuichi, Berry, Gerald J., Tait, Jonathan F., Strauss, H.William, Robbins, Robert C.
• Format: Journal Article
• Language: English
• Published: United States Mosby, Inc 01-11-1998; AATS/WTSA
• Subjects: Animals; Annexin A5; Apoptosis - drug effects; Apoptosis - physiology; Cyclosporine - pharmacology; Graft Rejection - diagnostic imaging; Graft Rejection - pathology; Heart Transplantation - immunology; Heart Transplantation - pathology; Immunosuppressive Agents - pharmacology; In Situ Nick-End Labeling; Male; Myocardium - immunology; Myocardium - pathology; Radionuclide Imaging; Rats; Rats, Inbred ACI; Rats, Inbred Strains; Sensitivity and Specificity; Technetium; Transplantation, Homologous
• ISSN: 0022-5223; 1097-685X
• DOI: 10.1016/S0022-5223(98)00446-2

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)