manganese(iii)tetraphenylporphine-sulfonate and Liver-Neoplasms

We investigated the interaction between manganese(III)mesoporphyrin (MnMeso), a metalloporphyrin, and liposome membranes containing oleic acid (OA; cis-9-octadecenoic acid). MnMeso associates preferentially with OA but minimally with egg phosphatidylcholine (EPC). Using small unilamellar vesicles, we characterized the MnMeso-OA binding at neutral pH. Our data suggest that MnMeso binds to the OA bilayer with Kd = 6.8 x 10(-4) M; the binding stoichiometry of MnMeso-OA was 1:3.4. This OA-MnMeso interaction was analyzed further for changes in the T1 relaxation property of MnMeso. OA increased the T1 of MnMeso significantly more than did EPC, suggesting that the OA-MnMeso interaction was stronger than that of PC-MnMeso. The side-chain specificity of the OA interaction with this porphyrin derivative was further supported in an experiment with manganese mesotetra(4-sulfonatophenyl)porphine, which lacks hydrophobic side chains for OA interaction. The association of MnMeso with the OA membrane was proposed according to the structure of MnMeso and OA and further verified using electron microscopy. A strong association of MnMeso with OA, an absorption enhancer of the gastrointestinal tract, may be useful for delivery of MnMeso as an oral contrast agent for magnetic resonance imaging.

Topics: Animals; Binding Sites; Contrast Media; Drug Carriers; Humans; Hydrogen-Ion Concentration; Intestinal Absorption; Lipid Bilayers; Liposomes; Liver Neoplasms; Magnetic Resonance Imaging; Manganese; Mesoporphyrins; Metalloporphyrins; Microscopy, Electron; Molecular Structure; Oleic Acids; Phosphatidylcholines; Rats

Manganese (III) mesoporphyrin (Mn-mesoporphyrin), a synthetic and stable complex, was investigated for its hepatic magnetic resonance imaging (MRI) properties and compared with manganese tetrakis-(4 sulfonatophenyl) porphyrin (Mn-TPPS4).. Liver abscesses (n = 10) and tumors (n = 14) were induced in rats. These rats then underwent MRI at 2.0 T. Animals received one of the two contrast agents, and measurement of lesion enhancement was performed.. At an intravenous dose of 0.035 mmol/kg, Mn-mesoporphyrin caused significant enhancement of normal liver parenchyma and increased the lesion-to-liver contrast in both the models of heptic liver abscess and metastatic liver disease. Mn-TTPS4 at an intravenous dose of 0.04 mmol/kg typically enhanced both lesion and normal liver parenchyma and therefore did not improve the lesion-to-liver contrast.. The hepatotrophic properties of Mn-mesoporphyrin indicate its potential as an intravenous contrast agent for liver imaging.

Topics: Animals; Contrast Media; Female; Liver Abscess; Liver Neoplasms; Magnetic Resonance Imaging; Mesoporphyrins; Metalloporphyrins; Rats; Rats, Inbred F344; Rats, Inbred Strains