title: Pharmacokinetics in melanoma-bearing mice of 5-dihydroxyboryl-6-propyl-2-thiouracil (BPTU), a candidate compound for boron neutron capture therapy.
abstract: Blood pharmacokinetics and tissue distribution of 5-dihydroxyboryl-6-propyl-2-thiouracil (BPTU), a boron carrier with postulated melanin-seeking properties for boron neutron capture therapy, were determined in C57/BL mice with subcutaneous pigmented or non-pigmented B16 melanomas. Borocaptate sodium (BSH) was used as a boron compound without melanin-seeking properties in a comparative biodistribution study in the same animal tumour models. Administration of single doses showed that BPTU was retained better in the pigmented B16 tumour than in the non-pigmented variant. BPTU was found in large concentrations in kidney and liver. Brain boron was approximately 10-fold lower than tumour boron. On a molar basis, BPTU demonstrated higher affinity for B16 tumours than BSH. Owing to solubility limits, tumour boron concentrations in this mouse study were too low for effective application of BNCT. However, the high tumour-to-blood and tumour-to-normal tissues ratios indicate that, with appropriate formulation, BPTU could be a promising candidate for clinical BNCT.
authors.affiliation: The Netherlands Cancer Institute, Division of Experimental Therapy, Amsterdam.
authors.forename: R
authors.initials: R
authors.lastname: Verrijk
authors.forename: I J
authors.initials: IJ
authors.lastname: Smolders
authors.forename: R
authors.initials: R
authors.lastname: Huiskamp
authors.forename: P R
authors.initials: PR
authors.lastname: Gavin
authors.forename: K H
authors.initials: KH
authors.lastname: Philipp
authors.forename: A C
authors.initials: AC
authors.lastname: Begg
mesh_terms: D000818:Animals; D001894:Borohydrides / Q000493:pharmacokinetics; D001896:Boron Compounds / Q000493:pharmacokinetics*; D016754:Boron Neutron Capture Therapy; D001932:Brain Neoplasms / Q000378:metabolism / Q000532:radiotherapy; D008543:Melanins / Q000378:metabolism; D008546:Melanoma, Experimental / Q000378:metabolism* / Q000532:radiotherapy*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011441:Propylthiouracil / Q000493:pharmacokinetics*; D012878:Skin Neoplasms / Q000378:metabolism / Q000532:radiotherapy; D013438:Sulfhydryl Compounds / Q000493:pharmacokinetics; D013889:Thiouracil / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D001894:Borohydrides; D001896:Boron Compounds; D008543:Melanins; D013438:Sulfhydryl Compounds; C014651:mercaptoundecahydrododecaborate; C060305:5-dihydroxyboryl-2-thiouracil; D013889:Thiouracil; D011441:Propylthiouracil