Persistent contrast enhancement by sterically stabilized paramagnetic liposomes in murine melanoma

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Abstract
In the present research, we investigated the use of paramagnetic liposomes as contrast agents (CAs) for the detection of solid tumors. The liposomes were sterically stabilized by a polyethylene glycol (PEG) coating, and their size was constrained to ∼100 nm. Dimyristoyl‐sn‐glycero‐3‐phosphoethanolamine‐N‐diethylene‐triaminepentaacetate (DMPE‐DTPA) was used as the gadolinium‐carrying fatty acid chain. The relaxation properties were characterized through nuclear magnetic relaxation dispersion (NMRD) measurements, and analyzed with the use of theories and computer programs that are adequate for slowly rotating systems. Their relaxivity at 1.5 T was found to be acceptable for in vivo use. We then tested the liposomes against B16‐F10 murine melanomas using standard T1‐weighted schemes at 1.5 T, and concentrations corresponding to 0.03 mmol/kg of gadolinium (i.e., three to six times lower than the concentration of the small gadolinium complexes in clinical use). The blood half‐life was found to be 120 ± 20 min. The experiments show a good contrast enhancement in the tumor (33% ± 22%) 2 hr after administration, a further increase (43 ± 27%) 20 hr after administration, and a decrease (25% ± 14%) 54 hr after administration. High persistence of the CA was also observed in the liver and intestine, as expected in a hepatobiliar excretion pathway. Magn Reson Med 52:669–672, 2004.