Boron neutron capture therapy demonstrated in mice bearing EMT6 tumors following selective delivery of boron by rationally designed liposomes

Proc Natl Acad Sci U S A. 2013 Apr 16;110(16):6512-7. doi: 10.1073/pnas.1303437110. Epub 2013 Mar 27.

Abstract

The application of boron neutron capture therapy (BNCT) following liposomal delivery of a (10)B-enriched polyhedral borane and a carborane against mouse mammary adenocarcinoma solid tumors was investigated. Unilamellar liposomes with a mean diameter of 134 nm or less, composed of an equimolar mixture of cholesterol and 1,2-distearoyl-sn-glycero-3-phosphocholine and incorporating Na3[1-(2'-B10H9)-2-NH3B10H8] in the aqueous interior and K[nido-7-CH3(CH2)15-7,8-C2B9H11] in the bilayer, were injected into the tail veins of female BALB/c mice bearing right flank EMT6 tumors. Biodistribution studies indicated that two identical injections given 24 h apart resulted in tumor boron levels exceeding 67 µg/g tumor at 54 h--with tumor/blood boron ratios being greatest at 96 h (5.68:1; 43 µg boron/g tumor)--following the initial injection. For BNCT experiments, tumor-bearing mice were irradiated 54 h after the initial injection for 30 min with thermal neutrons, resulting in a total fluence of 1.6 × 10(12) neutrons per cm(2) (±7%). Significant suppression of tumor growth was observed in mice given BNCT vs. control mice (only 424% increase in tumor volume at 14 d post irradiation vs. 1551% in untreated controls). In a separate experiment in which mice were given a second injection/irradiation treatment 7 d after the first, the tumor growth was vastly diminished (186% tumor volume increase at 14 d). A similar response was obtained for mice irradiated for 60 min (169% increase at 14 d), suggesting that neutron fluence was the limiting factor controlling BNCT efficacy in this study.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenocarcinoma / therapy*
  • Animals
  • Boranes / therapeutic use
  • Boron Neutron Capture Therapy / methods*
  • Female
  • Kaplan-Meier Estimate
  • Liposomes / metabolism
  • Liposomes / therapeutic use
  • Mammary Neoplasms, Experimental / therapy*
  • Mice
  • Phosphatidylcholines / administration & dosage
  • Phosphatidylcholines / therapeutic use*
  • Time Factors
  • Treatment Outcome

Substances

  • Boranes
  • Liposomes
  • Phosphatidylcholines
  • 1,2-distearoyllecithin