title: Total syntheses of three copper (II) tetracarboranylphenylporphyrins containing 40 or 80 boron atoms and their biological properties in EMT-6 tumor-bearing mice.
abstract: Three carboranyltetraphenylporphyrins containing 40 or 80 boron atoms were synthesized and evaluated for their biodistribution and toxicity in EMT-6 tumor-bearing mice. Copper (II) meso-5,10,15,20-tetrakis[3-methoxy-4-(o-carboranylmethoxy)phenyl]porphyrin, 6, and copper (II) meso-5,10,15,20-tetrakis[3-hydroxy-4-(o-carboranylmethoxy)phenyl]porphyrin, 8, are B40 congeners with different lipophilicities, each less than their B80 congener, copper (II) meso-5,10,15,20-tetrakis[m-(3,5-di-o-carboranylmethoxybenzyloxy)phenyl]porphyrin, 18. Two days after the last of a series of i.p. injections in BALB/c mice bearing EMT-6 mammary tumors, a dose of 185 mg/kg 6 (54 mg/kg B) delivered over 3.5 times the concentration of boron to tumor (169 microg/g B) than did 118 mg/kg 8 (36 mg/kg B), which delivered 35 microg/g B, or 87 mg/kg 18 (30 mg/kg B), which delivered 46 microg/g B. The tumor-to-blood and tumor-to-brain boron concentration ratios at that time for all three porphyrins exceeded 80:1. Two days after the last injection, there resulted moderate thrombocytopenia that essentially disappeared two days later from 6 and 18, and mild leukocytosis from 6, 8, and 18, all of which were clinically inconsequential. Thus, 6 may rank among the most clinically promising carboranyl porphyrins ever made to deliver 10B to tumors for boron neutron-capture therapy (BNCT) that has also been tested for its toxicity in vivo.
authors.affiliation: Medical Department, Building 490, Brookhaven National Laboratory, Upton, NY 11973-5000, USA.
authors.forename: Haitao
authors.initials: H
authors.lastname: Wu
authors.forename: Peggy L
authors.initials: PL
authors.lastname: Micca
authors.forename: Michael S
authors.initials: MS
authors.lastname: Makar
authors.forename: Michiko
authors.initials: M
authors.lastname: Miura
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics* / Q000633:toxicity; D001896:Boron Compounds / Q000138:chemical synthesis*; D045744:Cell Line, Tumor; D003300:Copper / Q000737:chemistry*; D004195:Disease Models, Animal; D004354:Drug Screening Assays, Antitumor; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism*; D008665:Metalloporphyrins / Q000138:chemical synthesis* / Q000493:pharmacokinetics* / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D013237:Stereoisomerism; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
chemical_list: D000970:Antineoplastic Agents; D001896:Boron Compounds; D008665:Metalloporphyrins; C513013:copper (II) meso-5,10,15,20-tetrakis(3-methoxy-4-(o-carboranylmethoxy)phenyl)porphyrin; D003300:Copper