title: Therapeutic efficacy of boron neutron capture therapy mediated by boron-rich liposomes for oral cancer in the hamster cheek pouch model.
abstract: The application of boron neutron capture therapy (BNCT) mediated by liposomes containing (10)B-enriched polyhedral borane and carborane derivatives for the treatment of head and neck cancer in the hamster cheek pouch oral cancer model is presented. These liposomes are composed of an equimolar ratio of cholesterol and 1,2-distearoyl-sn-glycero-3-phosphocholine, incorporating K[nido-7-CH3(CH2)15-7,8-C2B9H11] (MAC) in the bilayer membrane while encapsulating the hydrophilic species Na3[ae-B20H17NH3] (TAC) in the aqueous core. Unilamellar liposomes with a mean diameter of 83 nm were administered i.v. in hamsters. After 48 h, the boron concentration in tumors was 67 ± 16 ppm whereas the precancerous tissue contained 11 ± 6 ppm, and the tumor/normal pouch tissue boron concentration ratio was 10:1. Neutron irradiation giving a 5-Gy dose to precancerous tissue (corresponding to 21 Gy in tumor) resulted in an overall tumor response (OR) of 70% after a 4-wk posttreatment period. In contrast, the beam-only protocol gave an OR rate of only 28%. Once-repeated BNCT treatment with readministration of liposomes at an interval of 4, 6, or 8 wk resulted in OR rates of 70-88%, of which the complete response ranged from 37% to 52%. Because of the good therapeutic outcome, it was possible to extend the follow-up of BNCT treatment groups to 16 wk after the first treatment. No radiotoxicity to normal tissue was observed. A salient advantage of these liposomes was that only mild mucositis was observed in dose-limiting precancerous tissue with a sustained tumor response of 70-88%.
authors.affiliation: Comisión Nacional de Energía Atómica, B1650KNA San Martin, Buenos Aires, Argentina;
authors.forename: Elisa M
authors.initials: EM
authors.lastname: Heber
authors.affiliation: International Institute of Nano and Molecular Medicine, University of Missouri, Columbia, MO 65211; hawthornem@missouri.edu schwint@cnea.gov.ar.
authors.forename: M Frederick
authors.initials: MF
authors.lastname: Hawthorne
authors.affiliation: International Institute of Nano and Molecular Medicine, University of Missouri, Columbia, MO 65211;
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Kueffer
authors.affiliation: Comisión Nacional de Energía Atómica, B1650KNA San Martin, Buenos Aires, Argentina;
authors.forename: Marcela A
authors.initials: MA
authors.lastname: Garabalino
authors.affiliation: Comisión Nacional de Energía Atómica, B1650KNA San Martin, Buenos Aires, Argentina;
authors.forename: Silvia I
authors.initials: SI
authors.lastname: Thorp
authors.affiliation: Comisión Nacional de Energía Atómica, B1650KNA San Martin, Buenos Aires, Argentina;
authors.forename: Emiliano C C
authors.initials: EC
authors.lastname: Pozzi
authors.affiliation: Comisión Nacional de Energía Atómica, B1650KNA San Martin, Buenos Aires, Argentina;
authors.forename: Andrea
authors.initials: A
authors.lastname: Monti Hughes
authors.affiliation: International Institute of Nano and Molecular Medicine, University of Missouri, Columbia, MO 65211;
authors.forename: Charles A
authors.initials: CA
authors.lastname: Maitz
authors.affiliation: International Institute of Nano and Molecular Medicine, University of Missouri, Columbia, MO 65211;
authors.forename: Satish S
authors.initials: SS
authors.lastname: Jalisatgi
authors.affiliation: Idaho National Laboratory, Idaho Falls, ID 83415; and.
authors.forename: David W
authors.initials: DW
authors.lastname: Nigg
authors.affiliation: Comisión Nacional de Energía Atómica, B1650KNA San Martin, Buenos Aires, Argentina;
authors.forename: Paula
authors.initials: P
authors.lastname: Curotto
authors.affiliation: Comisión Nacional de Energía Atómica, B1650KNA San Martin, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas, 1033 Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Verónica A
authors.initials: VA
authors.lastname: Trivillin
authors.affiliation: Comisión Nacional de Energía Atómica, B1650KNA San Martin, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas, 1033 Ciudad Autónoma de Buenos Aires, Argentina hawthornem@missouri.edu schwint@cnea.gov.ar.
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Schwint
mesh_terms: D000818:Animals; D001895:Boron / Q000009:adverse effects / Q000494:pharmacology*; D016754:Boron Neutron Capture Therapy / Q000009:adverse effects / Q000379:methods*; D006224:Cricetinae; D004354:Drug Screening Assays, Antitumor; D008081:Liposomes; D008647:Mesocricetus; D009062:Mouth Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D009374:Neoplasms, Experimental / Q000473:pathology / Q000532:radiotherapy*; D013997:Time Factors
chemical_list: D008081:Liposomes; D001895:Boron
keywords: BNCT; boronated liposomes; cancer; neutron radiation; oncology