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

Journal Article · Tue Nov 11 00:00:00 EST 2014 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.1410865111· OSTI ID:1177640

Heber, Elisa M. ^[1]; Hawthorne, M. Frederick ^[2]; Kueffer, Peter J. ^[2]; Garabalino, Marcela A. ^[1]; Thorp, Silvia I. ^[1]; Pozzi, Emiliano C. C. ^[1]; Hughes, Andrea Monti ^[1]; Maitz, Charles A. ^[2]; Jalisatgi, Satish S. ^[2]; Nigg, David W. ^[3]; Curotto, Paula ^[1]; Trivillin, Verónica A. ^[1]; Schwint, Amanda E. ^[1]

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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)

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 at 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.

• Research Organization: Idaho National Lab. (INL), Idaho Falls, ID (United States)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC07-05ID14517
• OSTI ID: 1177640
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, Issue 45; ISSN 0027-8424
• Publisher: National Academy of Sciences, Washington, DC (United States)
• Country of Publication: United States
• Language: English

Related Subjects

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