MRI contrast enhancement of necrosis by MP-2269 and gadophrin-2 in a rat model of liver infarction

RATIONALE AND OBJECTIVES. The mechanisms of action leading to specific loca lization of necrosis-avid contrast agents (NACAs) such as gadophrin-2 are n ot well defined, It has been suggested recently that agents with a high deg ree of serum albumin binding may also serve as NACAs by virtue of nonspecif ic hydrophobic interactions. The present MRI-histomorphology correlation st udy was conducted to verify the likelihood of the proposed albumin-binding mechanism by comparing an albumin-binding blood pool agent, MP-2269, with g adophrin-2 in a rat model of reperfused liver infarction. METHODS. Reperfused infarction in the right liver lobe was surgically induc ed in six rats, Serial T1-weighted MRI was performed before and after intra venous injection of MP-2269 at 0.05 mmol/kg and repeated in the same rats 2 4 hours later after intravenous injection of gadophrin-2 at the same dosage (0.05 mmol/kg), The MR images were matched with corresponding histomorphol ogical findings. The signal intensity and contrast ratio of infarcted and n ormal hepatic lobes were quantified and compared between the two agents dur ing the postcontrast course. RESULTS. Before contrast, the infarcted lobe was indiscernible from normal liver on T1-weighted MRI, Shortly after injection of both MP-2269 and gadop hrin-2, a negative contrast occurred between infarcted and normal liver bec ause of a strong liver signal intensity enhancement and an inferior uptake in the necrotic liver. On delayed phase (>60 minutes), a necrosis-specific contrast enhancement (contrast ratio 1.6) developed with gadophrin-2 but no t with MP-2269, The MR images matched well with corresponding histomorpholo gical findings. CONCLUSIONS. Although both MP-2269 and gadophrin-2 feature an albumin-bindi ng capacity, only gadophrin-2 displayed a persistent necrosis-specific cont rast enhancement in the rat model of reperfused liver infarction, Therefore , the role of albumin binding in the mechanisms of NACAs should be reevalua ted.