Boron Compounds: New Candidates for Boron Carriers in BNCT
The high accumulation and selective delivery of 10B into the tumor tissue are the most important requirements to achieve efficient neutron capture therapy for cancer. So far, two boron compounds, sodium mercaptoundecahydrododecaborate (Na 2 10 B12H11SH; N
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Boron Compounds: New Candidates for Boron Carriers in BNCT Hiroyuki Nakamura and Mitsunori Kirihata
Contents 7.1
New Candidates for Boron Carriers in BNCT ........................................................... 99 7.1.1 Small Boron Molecules ...................................................................................... 100 7.1.2 Boron-Conjugated Biological Complexes .......................................................... 103
References ............................................................................................................................... 112
7.1
New Candidates for Boron Carriers in BNCT
The cell-killing effect of BNCT is due to the nuclear reaction of two essentially nontoxic species, boron-10 (10B) and thermal neutrons, whose destructive effect is well observed in boron-loaded tissues. Therefore, the high accumulation and selective delivery of 10B into the tumor tissue are the most important requirements to achieve efficient neutron capture therapy for cancer [1, 2]. In order to fatally damage tumor cells with BNCT, three important parameters should be considered in the development of boron carriers: (1) the boron concentrations in the tumor should be in the range of 20–35 mg 10B/g; (2) the tumor/normal tissue ratio should be greater than 3–5; and (3) the toxicity should be sufficiently low [3]. So far, two boron compounds, sodium mercaptoundecahydrododecaborate (Na210B12H11SH; Na210BSH) [4] and L-pboronophenylalanine (L-10BPA) [5], have been clinically utilized for the treatment of patients with malignant brain tumors [6] and malignant melanoma [7]. Recently, BNCT has been applied to various cancers, including head and neck cancer, lung H. Nakamura (*) Department of Chemistry, Faculty of Science, Gakushuin University, 1-5-1, Mejiro, Toshima-ku, Tokyo, 171-8588, Japan e-mail: [email protected] M. Kirihata Graduate School of Agriculture and Life Sciences, Osaka Prefecture University, Osaka, Japan e-mail: [email protected] W.A.G. Sauerwein et al. (eds.), Neutron Capture Therapy, DOI 10.1007/978-3-642-31334-9_7, © Springer-Verlag Berlin Heidelberg 2012
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cancer, hepatoma, chest wall cancer, and mesothelioma [8–10]. Therefore, the development of new boron carriers is one of the most important issues that should be resolved to extend the application of BNCT to various cancers. As the novel review written by Soloway and coworkers covered boron carriers reported until 1998 in detail [1], we review herein new and promising candidates for boron carriers developed in the last 10 years. In the last decade, boron carrier development has taken two directions: small boron molecules and boron-conjugated biological complexes. Unlike approaches using pharmaceuticals, boron carriers require high tumor selectivity and should be essentially nontoxic. Therefore, the latter approach has become one of the recent trends to accumulate a large amount of 10B in tumor tissues.
7.1.1
Small Boron Molecules
A small boron molecule
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