Acute liver rejection: evaluation with cell-directed MR contrast agents in a rat transplantation model

Abstract

Enhancement patterns with gadolinium (4s)-4-(4-ethoxybenzyl)-3,6,9-tris (carboxylatomethyl)-3,6,9-triazaundecandioic acid (EOB) diethylenetriaminepentaacetic acid (DTPA), a hepatocyte-directed magnetic resonance (MR) contrast agent, and superparamagnetic iron oxide particles (SPIO), a Kupffer cell-directed contrast agent, were compared at MR imaging in rat models of allogeneic and syngeneic liver transplantation. Light and electron microscopy were performed to monitor the morphologic changes in these livers and revealed typical findings in acute rejecting liver (allogeneic transplants) and normal architecture in syngeneic transplants. Liver enhancement with Gd-EOB-DTPA at MR imaging was delayed and prolonged with transplantation, and even more with rejection, but the level of enhancement when compared with that of control rats remained unaffected. Uptake of SPIO was decreased in the acutely rejecting livers but was normal in the syngeneic transplantation model. Enhanced MR imaging with cell-directed contrast agents depicted decreased phagocytotic activity in acute transplant rejection and enabled the excretory function of hepatocytes to be monitored. Additionally, Gd-EOB-DTPA may be applied advantageously for detection of focal lesions in transplanted livers.