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Metalloporphyrin Enhancement of Magnetic Resonance Imaging of Human Tumor Xenografts in Nude Mice¹

Department of Cell Biology, AMC Cancer Research Center, Denver, Colorado 80214

Paramagnetic metalloporphyrins were examined for their in vivo biodistribution and their ability to enhance nuclear magnetic resonance imaging of human tumor xenografts in nude mice. The metalloporphyrins tested were: manganese tetrasodium-meso-tetra(4-sulfonatophenyl)-porphine (MnTPPS); manganese meso-tetra-4-pyridylporphine; and gadolinium meso-tetra-4-pyridylporphine. All exhibited high molar relaxivities in aqueous solution. In vivo, at a dose of 2 mg/mouse, MnTPPS depressed the longitudinal relaxation time, T₁, significantly in the kidney and less in lung and blood. Manganese meso-tetra-4-pyridylporphine depressed T₁ in the kidney, lung and liver, while gadolinium meso-tetra-4-pyridylporphine caused large T₁ depressions in the blood, liver, brain and tumor, probably due to dissociation of the metalloporphyrin and binding of Gd to plasma or tissue proteins. At a dose of 10 mg/mouse, MnTPPS caused marked T₁ depressions of all tissues tested within 5 min of inoculation, but 48–72 h later, T₁ values of normal tissues had returned to near normal, while those of the tumors remained sigificantly depressed. MnTPPS was able to significantly enhance the intensity of nuclear magnetic resonance images of MX-1 and ZR-75 human breast tumors and CX-1 and LS174T human colon tumor xenografts in nude mice. The results demonstrate that paramagnetic metalloporphyrins, because of their high relaxivities and retention in tumors, have the potential for use as tumor-selective contrast agents for nuclear magnetic resonance imaging.

¹ Supported in part by a gift to the AMC Cancer Research Center from the Gannett Foundation.

² To whom requests for reprints should be addressed, at Department of Cell Biology, AMC Cancer Research Center, 1600 Pierce St., Denver, CO 80214.

Received 12/14/87. Revised 3/16/88. Accepted 5/20/88.

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