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 (≥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.