Radiolabeled annexin V imaging: Diagnosis of allograft rejection in an experimental rodent model of liver transplantation

PURPOSE: To assess the value of imaging rejection-induced apoptosis with te chnetium 99m and annexin V, a human protein-based radiopharmaceutical used in the diagnosis of acute rejection of a liver transplant, in a well-charac terized rodent model of orthotopic liver transplantation. MATERIALS AND METHODS: Tc-99m-radiolabeled annexin V was intravenously admi nistered to six allografted (immunologically mismatched) and five isografte d (immunologically matched) recipient rats on days 2, 4, and 7 after orthot opic 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 nucl ear 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 uptak e of annexin V on days 4 and 7, respectively. Severe acute rejection was hi stologically detected in all allografted livers on day 7. There was no hist ologic evidence of acute rejection in isografted animals. Dynamic hepatobil iary imaging with Tc-99m 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 sensiti ve and specific than imaging with Tc-99m-mebrofenin in the diagnosis of acu te rejection of a liver transplant.