EVALUATION OF CARBORANE-CONTAINING PORPHYRINS AS TUMOR TARGETING AGENTS FOR BORON NEUTRON-CAPTURE THERAPY

A number of carborane-containing porphyrins were administered to mice bearing subcutaneously transplanted mammary carcinomas. Administration was via serial intraperitoneal (ip) injections to assess their relati ve toxicities and tumour affinities. Three analogues of the natural po rphyrin heme and four tetraphenylporphyrins (TPPs) were given at total doses of 78-245 mu g g(-1) body weight. The water-insoluble TPPs were less toxic to mice, and delivered greater amounts of boron to tumour than did the water-soluble TPPs and the heme analogues. One such compo und, NiTCP-H, delivered more than 100 mu g B g(-1) to tumour tissue wi th a tumour:blood boron concentration ratio greater than 500:1 and a t umour:brain boron concentration ratio greater than 50:1, 4 days after the last of six ip injections given over 2 days. Another TPP analogue, NiTCP, delivered approximate to 50 mu g B g(-1) to tumour with simila r boron concentrations in normal tissues. Neither compound was toxic t o mice at total doses of approximate to 200 mu g g(-1) body weight. In contrast, the heme analogues were toxic and, with the exception of VC DP: delivered less boron to tumour than NiTCP and NiTCP-H. The two por phyrins with the greatest potential for application to boron neutron c apture therapy (BNCT), NiTCP and NiTCP-H, yielded higher tumour:blood and tumour:brain boron concentration ratios in mice than could be achi eved with p-boronophenylalanine (BPA) and sodium mercaptoundecahydrodo decaborate (BSH), the compounds which are currently being used in clin ical trials of BNCT in the treatment of glioblastoma. The boron delive red by each of the porphyrins tested remained. in tumour tissue longer than did boron delivered by either BPA or BSH. The copper and nickel chelates of these porphyrins behave identically in vivo. The former of fer the potential for imaging by Cu-67-mediated single photon emission computed tomography (SPECT) to aid BNCT treatment planning.