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Radiolabeled Annexin V Imaging: Diagnosis of Allograft Rejection in an Experimental Rodent Model of Liver Transplantation¹

¹ From the Depts of Surgery (Y.O., S.M.K., O.M.M., C.O.E.), Radiology/Div of Nuclear Medicine (S.K., H.W.S., F.G.B.), and Pathology (J.P.T.H.), Stanford University School of Medicine, Lucile Salter Packard Children's Hospital, 725 Welch Rd, Palo Alto, CA 94304; and Dept of Laboratory Medicine, University of Washington, Seattle (J.F.T.). Received Apr 14, 1999; revision requested May 10; final revision received Aug 6; accepted Aug 30. F.G.B. and H.W.S. supported in part by Children's Health Research Fund, Lucile Salter Packard Children's Hospital and by National Institutes of Health grant HL61717. J.F.T., O.M.M., and S.M.K. supported in part by National Institutes of Health grants HL-47151, DK47810, and AI35994, respectively. Y.O. supported in part by Stanford University School of Medicine Dean's Postdoctoral Fellowship. Address reprint requests to F.G.B. (e-mail: ma.frb@forsythe.standford.edu).

PURPOSE: To assess the value of imaging rejection-induced apoptosis with technetium 99m and annexin V, a human protein–based radiopharmaceutical used in the diagnosis of acute rejection of a liver transplant, in a well-characterized rodent model of orthotopic liver transplantation.

MATERIALS AND METHODS: ^99mTc-radiolabeled annexin V was intravenously administered to six allografted (immunologically mismatched) and five isografted (immunologically matched) recipient rats on days 2, 4, and 7 after orthotopic liver transplantation. Animals were imaged 1 hour after injection of 0.2–2.0 mCi (8.0–74.0 MBq) of radiolabeled annexin V by use of clinical nuclear scintigraphic equipment.

RESULTS: All animals in the allografted group demonstrated marked increases of 55% and 97% above the activity in the isografted group in hepatic uptake of annexin V on days 4 and 7, respectively. Severe acute rejection was histologically detected in all allografted livers on day 7. There was no histologic evidence of acute rejection in isografted animals. Dynamic hepatobiliary imaging with ^99mTc and mebrofenin, an iminodiacetic acid derivative, demonstrated no correlation with the presence or absence of acute rejection or with annexin V uptake.

CONCLUSION: Noninvasive imaging with radiolabeled annexin V is more sensitive and specific than imaging with ^99mTc-mebrofenin in the diagnosis of acute rejection of a liver transplant.

Index terms: Animals • Annexin V • Liver, radionuclide studies, 761.12172, 761.458 • Liver, transplantation, 761.12172, 761.458 • Mebrofenin • Radionuclide imaging, experimental studies, 761.12172, 761.458

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