Detection and characterization of primary liver cancer in rats by MS-264-enhanced MRI

A new MR contrast agent, MS-264 (Gd(1RS)-1-(p-butylbenzyl)-DTPA), was developed to achieve hepatobiliary specificity and its potential evaluated for detecting and characterizing liver tumors in rats with chemically induced hepatocellular carcinoma (HCC). In seven rats with 66 HCC lesions, enhancements of different abdominal organs and tumors were compared on T1-weighted images after intravenous administration of Gd-DTPA (0.3 mmol/kg) and MS-264 (0.05 mmol/kg). MR images were correlated with postmortem microangiographic and histological findings. An overall enhancement of different organs, which normalized within 24 h, was observed after Gd-DTPA and MS-264 injection. MS-264 caused a higher relative enhancement (RE) in liver (60%), compared with that of Gd-DTPA (40%), which resulted in a prompt negative contrast enhancement in 59 of 66 HCCs. All were moderately to poorly differentiated (Grades II-IV) tumors. Six of these 59 negative contrast-enhancing lesions showed a positively enhanced peritumoral rim, which corresponded histologically to malignant infiltration (n = 2) or compression (n = 4). On the other hand, six well differentiated HCCs showed prolonged positive enhancement. However, one well differentiated HCC was not positively enhanced by MS-264, probably due to poor access of the agent to the lesion. In comparison to that of the precontrast images, enhancement with Gd-DTPA and MS-264 increased the number of detected lesions by 22 and 42%, respectively. In this animal study, MS-264 proved to be useful in detection and characterization of primary liver cancers.status: publishe

Localization of metalloporphyrin-induced "specific" enhancement in experimental liver tumors: Comparison of magnetic resonance imaging, microangiographic, and histologic findings

Rationale and objectives We investigated the tumor specificity of gadolinium mesoporphyrin (Gd-MP) and manganese tetraphenylporphyrin (Mn-TPP) as magnetic resonance (MR) imaging contrast agents. Methods Fifteen rats with multiple hepatocellular carcinomas and eight rats with implanted Novikoff hepatomas were given intravenous injections of either Gd-MP or Mn-TPP at 0.05 mmol/kg, which was compared with nonspecific gadopentetate dimeglumine (0.3 mmol/kg). T1-weighted spin-echo images were obtained before and up to 48 hr after injection and compared with corresponding microangiograms and histologic specimens. The relative enhancement of organs and tumors was plotted as a function of time. Results Initially, both metalloporphyrins behaved as nonspecific agents, similar to gadopentetate dimeglumine, and enhanced the tumor by perfusion and diffusion. However, metalloporphyrins, but not gadopentetate dimeglumine, caused a delayed (> or = 3 hr) enhancement in some compartments of certain lesions. The MR imaging-microangiography-histology matching technique revealed that those compartments were actually nonviable components, including necrosis (n = 10), thrombosis (n = 7), and cystic secretion (n = 3), but not viable tumor tissue. Conclusion Metalloporphyrins did not prove to be tumor specific. However, the observed affinity for nonviable tissue has elicited other potential applications for these agents.status: publishe