title: Boron neutron capture therapy demonstrated in mice bearing EMT6 tumors following selective delivery of boron by rationally designed liposomes.
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.
authors.affiliation: International Institute of Nano and Molecular Medicine, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Kueffer
authors.forename: Charles A
authors.initials: CA
authors.lastname: Maitz
authors.forename: Aslam A
authors.initials: AA
authors.lastname: Khan
authors.forename: Seth A
authors.initials: SA
authors.lastname: Schuster
authors.forename: Natalia I
authors.initials: NI
authors.lastname: Shlyakhtina
authors.forename: Satish S
authors.initials: SS
authors.lastname: Jalisatgi
authors.forename: John D
authors.initials: JD
authors.lastname: Brockman
authors.forename: David W
authors.initials: DW
authors.lastname: Nigg
authors.forename: M Frederick
authors.initials: MF
authors.lastname: Hawthorne
mesh_terms: D000230:Adenocarcinoma / Q000628:therapy*; D000818:Animals; D001880:Boranes / Q000627:therapeutic use; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D005260:Female; D053208:Kaplan-Meier Estimate; D008081:Liposomes / Q000378:metabolism / Q000627:therapeutic use; D008325:Mammary Neoplasms, Experimental / Q000628:therapy*; D051379:Mice; D010713:Phosphatidylcholines / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001880:Boranes; D008081:Liposomes; D010713:Phosphatidylcholines; C010942:1,2-distearoyllecithin
references.citation: Radiother Oncol. 2008 Aug;88(2):183-91
references.pmid: 18336940
references.citation: Adv Drug Deliv Rev. 2011 Mar 18;63(3):136-51
references.pmid: 20441782
references.citation: Br J Cancer. 1985 Feb;51(2):211-8
references.pmid: 3966978
references.citation: Science. 1997 Mar 14;275(5306):1649-52
references.pmid: 9054359
references.citation: Biochemistry. 1990 May 22;29(20):4929-39
references.pmid: 2163672
references.citation: Clin Cancer Res. 2005 Jun 1;11(11):3987-4002
references.pmid: 15930333
references.citation: Appl Radiat Isot. 2009 Jul;67(7-8 Suppl):S222-5
references.pmid: 19410474
references.citation: Proc Natl Acad Sci U S A. 1999 May 25;96(11):6406-10
references.pmid: 10339600
references.citation: Br J Radiol. 1998 Mar;71(843):320-3
references.pmid: 9616243
references.citation: Inorg Chem. 1999 Nov 1;38(22):4926-4927
references.pmid: 11671232
references.citation: Cancer Res. 2001 Dec 15;61(24):8775-81
references.pmid: 11751398
references.citation: Inorg Chem. 1996 Sep 11;35(19):5412-5416
references.pmid: 11666725
references.citation: Chem Commun (Camb). 2002 Mar 21;(6):547-54
references.pmid: 12120120
references.citation: J Neurooncol. 1997 May;33(1-2):19-26
references.pmid: 9151220
references.citation: J Neurooncol. 1997 May;33(1-2):53-8
references.pmid: 9151223
references.citation: Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1367-70
references.pmid: 7877984
references.citation: Radiat Res. 2001 Apr;155(4):603-10
references.pmid: 11260662
references.citation: Int J Radiat Oncol Biol Phys. 1996 Mar 15;34(5):1081-6
references.pmid: 8600091
references.citation: J Neurooncol. 2003 Mar-Apr;62(1-2):101-9
references.pmid: 12749706
references.citation: Cancer Res. 1986 Dec;46(12 Pt 1):6387-92
references.pmid: 2946403
references.citation: J Inorg Biochem. 2008 Apr;102(4):943-51
references.pmid: 18255155
references.citation: Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3029-33
references.pmid: 8159700
references.citation: Cell. 1983 Apr;32(4):1069-79
references.pmid: 6404557
references.citation: Pharmacol Rev. 2006 Mar;58(1):32-45
references.pmid: 16507881
references.citation: Appl Radiat Isot. 2011 Dec;69(12):1756-9
references.pmid: 21543233
references.citation: Int J Radiat Oncol Biol Phys. 2012 Jan 1;82(1):e67-75
references.pmid: 21300462
references.citation: Appl Radiat Isot. 2011 Dec;69(12):1790-2
references.pmid: 21565517
references.citation: Appl Radiat Isot. 2011 Dec;69(12):1737-40
references.pmid: 21482122
references.citation: Radiat Res. 1999 Jan;151(1):1-18
references.pmid: 9973079
references.citation: Biochemistry. 1993 Jan 26;32(3):889-99
references.pmid: 8422393
references.citation: Br J Cancer. 1976 Mar;33(3):320-8
references.pmid: 57788
references.citation: Radiat Environ Biophys. 2012 May;51(2):195-204
references.pmid: 22271404
references.citation: Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9039-43
references.pmid: 1409600
references.citation: J Neurooncol. 2003 Mar-Apr;62(1-2):111-21
references.pmid: 12749707
references.citation: Chem Rev. 1998 Jun 18;98(4):1515-1562
references.pmid: 11848941
references.citation: Am J Pathol. 2002 Feb;160(2):403-8
references.pmid: 11839558
references.citation: J Neurooncol. 2003 Mar-Apr;62(1-2):33-45
references.pmid: 12749701
references.citation: Mol Med Today. 1998 Apr;4(4):174-81
references.pmid: 9572059