title: In vivo evaluation of phosphorous-containing derivatives of dodecahydro-closo-dodecaborate for boron neutron capture therapy of gliomas and sarcomas.
abstract: The in vivo uptake of dodecahydro-closo-dodecaborate derivatives substituted with phosphate- and bisphosphonate groups was evaluated in two different experimental tumor model systems and compared to other boronated and non-boronated compounds. These phosphorous-containing boron clusters may have potential for use in boron neutron capture therapy, a chemoradiotherapeutic form of cancer treatment. Using the F98 rat glioma as a brain tumor model in syngeneic Fischer rats, there was selective tumor uptake of the phosphate derivative with 21.5 micrograms boron/g tumor versus 5.2 micrograms/g normal brain and a tumor:blood ratio of 2.7. However, this compound was toxic to test animals and lethal at relatively low doses. The uptake of the bisphosphonate by the murine K8 osteosarcoma was approximately 18 micrograms boron/g tumor with a T:Bl ratio of 7.6 and a tumor:bone ratio of 1.5. This compound was non toxic to the test animals. The results indicate that phosphate- and bisphosphonate derivatives of dodecahydro-closo-dodecaborate may have potential for BNCT of gliomas and osteosarcomas, respectively.
authors.affiliation: College of Pharmacy, Ohio State University, 500 W. 12th Ave, Columbus, Ohio 43210, USA. tjarks.1@osu.edu
authors.forename: W
authors.initials: W
authors.lastname: Tjarks
authors.forename: R F
authors.initials: RF
authors.lastname: Barth
authors.forename: J H
authors.initials: JH
authors.lastname: Rotaru
authors.forename: D M
authors.initials: DM
authors.lastname: Adams
authors.forename: W
authors.initials: W
authors.lastname: Yang
authors.forename: R G
authors.initials: RG
authors.lastname: Kultyshev
authors.forename: J
authors.initials: J
authors.lastname: Forrester
authors.forename: B A
authors.initials: BA
authors.lastname: Barnum
authors.forename: A H
authors.initials: AH
authors.lastname: Soloway
authors.forename: S G
authors.initials: SG
authors.lastname: Shore
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism / Q000532:radiotherapy*; D001896:Boron Compounds / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D001932:Brain Neoplasms / Q000378:metabolism / Q000532:radiotherapy*; D004164:Diphosphonates; D005910:Glioma / Q000378:metabolism / Q000532:radiotherapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000532:radiotherapy; D012516:Osteosarcoma / Q000378:metabolism / Q000532:radiotherapy*; D010710:Phosphates; D017553:Phosphorus Compounds / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D051381:Rats; D011916:Rats, Inbred F344; D013669:Technetium Tc 99m Medronate; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
chemical_list: D001896:Boron Compounds; D004164:Diphosphonates; D010710:Phosphates; D017553:Phosphorus Compounds; D013669:Technetium Tc 99m Medronate