BNCT is based on the nuclear capture and fission reactions that occur when nonradioactive boron-10 is irradiated with low energy thermal neutrons to yield LET alpha particles (4He) and recoiling lithium-7 (7Li) nuclei. For BNCT to be successful, a sufficient number of 10B atoms (approximately 109 atoms/cell) must be selectively delivered to the tumor and enough thermal neutrons must be absorbed by them to sustain a lethal 10B(n,a) 7Li capture reaction. BNCT primarily has been used to treat patients with brain tumors, and more recently those with head-and-neck cancer. Two LMW boron delivery agents currently are being used clinically, BSH and BPA. However, a variety of HMW agents consisting of macromolecules and nanovehicles have been developed. This review focuses on the latter, which includes mAbs, dendrimers, liposomes, dextrans, polylysine, avidin, FA, and both epidermal and vascular endothelial growth factors (EGF and VEGF). Procedures for introducing boron atoms into these HMW agents and their chemical properties are discussed. In vivo studies on their biodistribution are described, and the efficacy of a subset of them, those which have been used for BNCT of tumors in experimental animals, will be discussed.

Because brain tumors currently are the primary candidates for treatment by BNCT, delivery of these HMW agents across the BBB presents a special challenge. Various routes of administration are discussed, including receptor-facilitated transcytosis following i.v. administration, direct i.t injection and convection-enhanced delivery in which a pump is used to apply a pressure gradient to establish bulk flow of the HMW agent during interstitial infusion. Finally, we have concluded with a discussion relating to issues that must be addressed if these HMW agents are to be used clinically.

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