BNCT: Boron Compounds

Current Boron Agents: BPA and BSH


In 1987, a Japanese dermatologist Dr. Mishima and his co-workers at Kobe University found that p-boronophenylalanine (BPA) is a suitable boron-delivery agent for BNCT to treat patients with cutaneous melanomas.

The structure of BPA

The structure of BPA highly resembles phenylalanine, a basic cell metabolite, which is often required by tumor cells at a much higher intake rate due to their rapid proliferative nature. BPA is believed to be transported by ATB0,+, LAT-1, and LAT transporters.
Although it contains multiple hydrogen-bonding elements, BPA is surprisingly difficult to dissolve in water. Later, it was found that fructose could form a stable complex with BPA that dramatically improves the solubility of BPA in water (about 100 g/l).4 Since then, BPA-fructose has emerged as one of the most commonly used formulations in the clinical studies of BNCT. To date, other polyols such as sorbitol or poly(vinyl alcohol) are used in complex with BPA. 

The structure of (a) BPA-fructose; (b) BPA-sorbitol, and (c) BPA-PVA


The first clinically used boron agent is sodium borocaptate (Na2B12H11SH, commonly known as BSH), whose structure is unique regular icosahedron of twelve boron atoms.

The structure of BSH

In 1967, Dr. Hatanaka and co-workers first reported the great potential of BSH as a boron agent for treatment of brain tumor. As early as next year, a team led by Hatanaka succeeded in treating patients with high grade glioma by administering BSH to them.
Although the pioneering work above suggested efficacy of BNCT, the success relied on the penetration of BSH to tumor through dysfunctional brain-blood barrier. In other words, BSH itself doesn’t actively accumulate into tumor. To achieve high accumulation of BSH to tumor tissues, a wide variety of boron carriers have been developed, such as BSH-containing distearoyl lipid liposomes (DSBL, Figure 2a),3 a block polymer PEG-b-P(Glu-SS-BSH) that forms polymeric micelles (Figure 2b).4 These nanomaterials can deliver high concentration of boron to tumor issues due to their enhanced permeability and retention (EPR) effect. Further developments to establish efficient boron delivery systems are still in high demand.

The structure of (a) DSBL; (b) PEG-b-P (Glu-SS-BSH)
In 1967, Soloway and Hatanaka
In 1967, Soloway and Hatanaka
First Use:
In 1989, Mishima: Treatment of Melanoma
First Use:
In 1989, Mishima: Treatment of Glioma
Chemical Characteristics:
A Derivative of Tyrosine
Selective Accumulation in Cancer Cells via LAT-1 (L-type Amino acid Transporter 1)
Chemical Characteristics:
Boron cluster containing 12 boron atoms
Non-Selective Accumulation in Cancer Cells 



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