PT  - JOURNAL ARTICLE
AU  - S Kamei
AU  - H Okada
AU  - Y Inoue
AU  - T Yoshioka
AU  - Y Ogawa
AU  - H Toguchi
TI  - Antitumor effects of angiogenesis inhibitor TNP-470 in rabbits bearing VX-2 carcinoma by arterial administration of microspheres and oil solution.
DP  - 1993 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 469--474
VI  - 264
IP  - 1
4099  - http://jpet.aspetjournals.org/content/264/1/469.short
4100  - http://jpet.aspetjournals.org/content/264/1/469.full
SO  - J Pharmacol Exp Ther1993 Jan 01; 264
AB  - 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.