VM-GD

In previous experiments in tumors we demonstrated that metalloporphyrins are particularly avid for nonviable tumor components. This study was performed to find out whether these agents can be used as MRI contrast agents for the visualization of acute myocardial infarction (MI). A total of 44 rats, 6 normal controls and 38 with occlusive MI (2-24 h old), were used. Gadolinium mesoporphyrin (Gd-MP) or manganese tetraphenylporphyrin (Mn-TPP) was intravenously injected at doses of 0.1, 0.05, and 0.01 mmol/kg. Three to 24 h after injection, axial and coronal T1-weighted (TR/TE 300/15 ms) spin-echo MR images were obtained before and after killing the animals and correlated with triphenyl tetrazolium chloride (TTC) histochemical preparations. The Gd-MP content in infarcted and noninfarcted myocardium was measured using inductively coupled plasma atomic emission spectroscopy (ICP-AES). MRI without contrast media could not discern the MI. However, 3-24 h after injection of either Gd-MP or Mn-TPP, the infarcted area was positively stained on MR images. This area matched well with the negatively TTC-stained area on the heart slices (r = 0.97). The contrast ratios between the infarcted necrotic myocardium and the noninfarcted regions varied from 150 to 300% depending on the type of agents and doses used. Neither false-positive nor false-negative findings were encountered. The metalloporphyrin concentration was more than 10 times higher in the infarcted than in the noninfarcted heart. Metalloporphyrins appear to be promising MRI contrast agents for detection and quantification of necrosis in MI. These preclinical results may open new perspectives in cardiac imaging.

We investigated the tumor specificity of gadolinium mesoporphyrin (Gd-MP) and manganese tetraphenylporphyrin (Mn-TPP) as magnetic resonance (MR) imaging contrast agents.

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.

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.

Metalloporphyrins did not prove to be tumor specific. However, the observed affinity for nonviable tissue has elicited other potential applications for these agents.