title: Selectivity of boron carriers for boron neutron capture therapy: pharmacological studies with borocaptate sodium, L-boronophenylalanine and boric acid in murine tumors.
abstract: Borocaptate sodium (BSH) and L-boronophenylalanine (L-BPA) are two boron carriers used for boron neutron capture therapy (BNCT) in the treatment of glioblastoma and melanoma, respectively. The suitability of these two compounds was evaluated on the basis of pharmacokinetic studies aiming at characterizing their biodistribution, tumor uptake and tumor selectivity. Boric acid was also used as a reference compound since it is nonselective and relatively freely diffusible. The compounds were investigated in two tumor models, a B16 pigmented melanoma and the RIF1 sarcoma. Mice were sacrificed after different boron doses at various post-injection times and tissue and plasma levels measured using inductively coupled plasma atomic emission spectroscopy (ICP-AES). The proposed minimum effective tumor boron concentration of 15 ppm was achieved in both tumor models for the three compounds tested, although only for L-BPA in the melanoma was this achieved when tumor-plasma ratios were above 1. In the RIF1 model, maximum tumor concentrations of 44 and 31 ppm B were reached after administration of 50 micrograms B/g body weight for boric acid and BSH, respectively. After administration of 12.5 micrograms B/g of L-BPA, maximum concentrations of 15 and 21 ppm were found in the RIF1 and B16 models, respectively. Tumor-plasma ratios (TPR) for BSH remained close to or below unity at all times studied in both tumors. Brain levels of BSH were very low, however, leading to tumor-brain ratios markedly greater than 1 at all times. L-BPA and boric acid showed TPR values above unity in both tumor models, reaching 3.2 in B16.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam.
authors.forename: V
authors.initials: V
authors.lastname: Gregoire
authors.forename: A C
authors.initials: AC
authors.lastname: Begg
authors.forename: R
authors.initials: R
authors.lastname: Huiskamp
authors.forename: R
authors.initials: R
authors.lastname: Verrijk
authors.forename: H
authors.initials: H
authors.lastname: Bartelink
mesh_terms: D000818:Animals; D001888:Boric Acids / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001894:Borohydrides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D001896:Boron Compounds / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016754:Boron Neutron Capture Therapy; D001921:Brain / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000378:metabolism / Q000532:radiotherapy*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D010649:Phenylalanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012513:Sarcoma, Experimental / Q000378:metabolism / Q000532:radiotherapy*; D013438:Sulfhydryl Compounds / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D013997:Time Factors
chemical_list: D001888:Boric Acids; D001894:Borohydrides; D001896:Boron Compounds; D011838:Radiation-Sensitizing Agents; D013438:Sulfhydryl Compounds; C014651:mercaptoundecahydrododecaborate; D010649:Phenylalanine; C032688:boric acid; C033685:4-boronophenylalanine