Tumor targeting by arterial administration of lipids: rabbit model with VX2 carcinoma in the liver.

We previously found that a lipid contrast medium, Lipiodol, remained selectively in liver tumors for a prolonged time after injection via the hepatic artery. We now extend this technique to other lipids including linoleic acid, olive oil, tea seed oil, and medium-chain triglyceride (MCT). MCT is a semisynthetic triglyceride with a lower viscosity than that of the other lipids. Each lipid was mixed with 14C linoleic acid, and the mixture with or without anticancer agent smancs was injected via the proper hepatic artery of rabbits with VX2 carcinoma in the liver. The 14C count in the tumor tissue was always more than 100 times that of the plasma or kidney, and the radioactivity 15 min after injection of MCT was more than 2500 times greater than that of blood plasma. At 24 hr after injection, the radioactivity recovered in the tumor was 4.9-37.0% (average 19.6%) of the dose, which indicated the greatest retention in the tumor tissue; there was rapid clearance from the rest of the body primarily via the bile. Advantages of the administration of lipid-solubilized drugs are: (i) remarkable tumor-selective targeting (a decisive anticancer effect with fewer side effects); (ii) prolonged drug retention (resulting in infrequent administration); (iii) various choices of different fatty acids with various pharmacokinetic characteristics as the carriers of the anticancer agents; and (iv) arterial administration is practicable in most hospitals.