TY - JOUR T1 - Antitumor effects of angiogenesis inhibitor TNP-470 in rabbits bearing VX-2 carcinoma by arterial administration of microspheres and oil solution. JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 469 LP - 474 VL - 264 IS - 1 AU - S Kamei AU - H Okada AU - Y Inoue AU - T Yoshioka AU - Y Ogawa AU - H Toguchi Y1 - 1993/01/01 UR - http://jpet.aspetjournals.org/content/264/1/469.abstract N2 - The antitumor activities of an angiogenesis inhibitor, (3R,4S,5S,6R)-5- methoxy-4-[(2R,3R)-2-methyl-3-(3-methyl-2-butenyl)-oxiranyl]-1- oxaspiro[2,5]oct-6-yl(chloroacetyl) carbamate (TNP-470), administered s.c., i.v. and intra-arterially using a chemoembolization technique, were examined in rabbits bearing VX-2 carcinoma. Repeated s.c. injection of TNP-470 aqueous solution clearly inhibited the tumor growth in proportion to the dose, and improved efficacy was obtained with once a week s.c. administration of microspheres, which provide sustained release of TNP-470. Moreover, the injection of the TNP-470 microspheres into the predominant artery of the tumor via a catheter, chemoembolization, resulted in dramatic regression of the tumor. This antitumor effect was enhanced by coadministration of doxorubicin hydrochloride aqueous solution. Arterial administration of TNP-470 oil solution provided more persistent tumor growth inhibition due to the prolonged release and targeting of the angiogenesis inhibitor to the tumor. ER -