ANTITUMOR EFFECT OF ARTERIAL ADMINISTRATION OF A MEDIUM-CHAIN TRIGLYCERIDE SOLUTION OF AN ANGIOGENESIS INHIBITOR, TNP-470, IN RABBITS BEARING VX-2 CARCINOMA

Using rabbits bearing VX-2 carcinoma on the inner side of the leg, we examined the antitumor activity of a medium-chain triglyceride (MCT) s olution of an angiogenesis inhibitor, TNP-470 (AGM-1470, 6-O-(N-chloro acetylcarbamoyl)-fumagillol, following administration into the femoral artery feeding the tumor, The MCT solution of TNP-470 (1 and 5 mg) st rongly suppressed tumor growth following a single intra-arterial (i. a .) injection 2 or 3 weeks after tumor inoculation. Moreover, remarkabl e regression of well-developed tumors, those 4 weeks after inoculation , was obtained by i. a. injection of the MCT solution containing 20 mg of TNP-470 without any influence on body weight. The antitumor effect s were potentiated by coadministration of doxorubicin or mitomycin C ( MMC) in the solution or microspheres containing MMC. In a shell-less c horioallantoic membrane (CAM) assay, angiogenesis was inhibited when a droplet of the MCT solution containing 25 mu g of TNP-470 was placed on the CAM for 2 days, suggesting that the prolonged antitumor effect resulted from the inhibition of tumor neovascularization by sustained drug release from the preparation. These results indicate that i. a. i njection of the MCT solution of TNP-470 is promising for treating well -developed tumors.