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Title: Therapeutic efficacy of boron neutron capture therapy mediated by boron-rich liposomes for oral cancer in the hamster cheek pouch model

Unilamellar liposomes formulated with an equimolar mixture of cholesterol and 1,2-distearoyl-sn-glycero-3-phosphocholine, incorporating K[nido-7-CH3(CH2)15-7,8-C2B9H11] in the lipid bilayer, and encapsulating Na3[1-(2’-B10-H9)-2-NH3B10H8] were prepared by probe sonication and investigated in vivo. Microwave assisted digestion followed by inductively coupled plasma-optical emission spectroscopy was utilized to determine the biodistribution of boron in various tissues following either a single tail vein injection or two identical injections (separated by 24 hours) of the liposomal suspension in BALB/c mice bearing EMT6 mammary adenocarcinomas in their right flank. Double-injection protocols resulted in a boron content in the tumor exceeding 50 µg of boron per gram of tissue for 48 to 72 hours subsequent to the initial injection while tumor:blood boron ratios were more ideal from 54 hours (1.9:1) to 96 hours (5.7:1) subsequent to the initial injection. Tumor bearing mice were given a double-injection of liposomes containing the 10B-enriched analogs of the aforementioned agents and subjected to a 30 minute irradiation by thermal neutrons with a flux of 8.8 x 108 (±7%) neutrons/cm2 s integrated over the energy range of 0.0 – 0.414 eV. Significant tumor response for a single BNCT treatment was demonstrated by growth curves versus a control group. Vastly diminished tumor growth was witnessed atmore » 14 days (186% increase versus 1551% in controls) in mice that were given a second injection/radiation treatment 7 days after the first. Mice given a one hour neutron irradiation following the double-injection of liposomes had a similar response (169% increase at 14 days) suggesting that neutron fluence is the limiting factor towards BNCT efficacy in this study.« less
Authors:
 [1] ;  [2] ;  [2] ;  [1] ;  [1] ;  [1] ;  [1] ;  [2] ;  [2] ;  [3] ;  [1] ;  [1] ;  [1]
  1. Comision Nacional de Energia Atomica (CNEA), Buenos Aires (Argentina)
  2. Univ. of Missouri, Columbia, MO (United States). International Inst. of Nano and Molecular Medicine
  3. Idaho National Lab. (INL), Idaho Falls, ID (United States)
Publication Date:
OSTI Identifier:
1177640
DOE Contract Number:
AC07-05ID14517
Resource Type:
Journal Article
Resource Relation:
Journal Name: Proceedings of the National Academy of Sciences of the United States of America; Journal Volume: 111; Journal Issue: 45
Publisher:
National Academy of Sciences, Washington, DC (United States)
Research Org:
Idaho National Laboratory (INL), Idaho Falls, ID (United States)
Sponsoring Org:
USDOE
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; NEUTRON CAPTURE THERAPY; THERMAL NEUTRONS; BORON; MICE; INJECTION; Biological Models; Milli EV RANGE; MICROWAVE RADIATION; CARCINOMAS; ANIMAL TISSUES; LIPOSOMES; BORON 10; EMISSION SPECTROSCOPY; IRRADIATION; IN VIVO; NEUTRON FLUENCE; PLASMA Boron Neutron Capture Therapy; equimolar mixture of cholesterol and 1,2-distearoy; Unilamellar liposomes