Magnetic resonance imaging (MRI) is an important tool in diagnostic radiology, and allows discrimination between a growth and surrounding soft tissue. The contrast depends of the relaxation times (T1 and T2) of the bulk water in the respective tissues. A paramagentic substance is one that contains an unpaired electron and alters the relaxation rate of water. Our objective is to identify a class of paramagentic contrast agents which are selectively retained by tumors, in order to facilitate and clarify MRI tumor contrast. We have chosen the water-soluble metalloporphyrins (WSMPs) for several reasons: porphyrins are known to be selectively retained by tumors, they form complexes with metal ions, and the synthetic water soluble porphyrins are much more tractable than the hydrophobic natural heme products. We have evaluated several of these WSMPs by several criteria: solubility; relaxivity; stability in human plasma and in vivo; distribution in vivo; toxicity; and MRI contrast properties. As a result of these comparisons we have identified Mn(III) TPPS as a potential tumor contrast agent in MRI. We are currently studying the mechanism of tumor retention and stability of porphyrins and WSMPs, and quantitative dose-contrast relationships in MRI of nude mice and rat tumors for a series of SMPs.
