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Advancements in Tumor Targeting Strategies for Boron Neutron Capture Therapy

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Abstract

Boron neutron capture therapy (BNCT) is a promising cancer therapy modality that utilizes the nuclear capture reaction of epithermal neutrons by boron-10 resulting in a localized nuclear fission reaction and subsequent cell death. Since cellular destruction is limited to approximately the diameter of a single cell, primarily only cells in the neutron field with significant boron accumulation will be damaged. However, the emergence of BNCT as a prominent therapy has in large part been hindered by a paucity of tumor selective boron containing agents. While L-boronophenylalanine and sodium borocaptate are the most commonly investigated clinical agents, new agents are desperately needed due to their suboptimal tumor selectivity. This review will highlight the various strategies to improve tumor boron delivery including: nucleoside and carbohydrate analogs, unnatural amino acids, porphyrins, antibody-dendrimer conjugates, cationic polymers, cell-membrane penetrating peptides, liposomes and nanoparticles.

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Abbreviations

10B:

Boron-10

18F-BPA:

4-borono-2-18F-fluoro-phenylalanine

BBB:

Blood–brain barrier

BNCT:

Boron neutron capture therapy

CPP:

Cell-membrane penetrating peptide

DNA:

Deoxyribonucleic Acid

EGFR:

Epidermal growth factor receptor

EPR:

Enhanced Permeability and Retention effect

157Gd:

Gadolinium-157

GdNCT:

Gadolinium neutron capture therapy

GBM:

Glioblastoma multiforme

ABCPC:

1-amino-3-boronocyclopentanecarboxylic acid

BPA:

L-boronophenylalanine

BSH:

Sodium borocaptate

H2PzCOB:

1-methyl-o-closocarboranyl-2-hexylthioporphyrazine

i.v.:

Intravenous

L-DOPA:

L-3,4-dihydroxyphenylalanine

LCOB:

o-closocarboranyl β-lactoside

mAbs:

Monoclonal antibodies

NPs:

Nanoparticles

PET:

Positron Emission Tomography

RES:

Reticuloendothelial system (RES)

H2TCP:

Tetra-(4-nido-carboranylphenyl) porphyrin

T/B:

Tumor/blood

T/N:

Tumor/normal tissue

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  1. Department of Radiation Oncology, Cancer Biology Division, Washington University in Saint Louis School of Medicine, 4511 Forest Park Ave., Room 3103, St. Louis, Missouri, 63108, USA

    Micah John Luderer, Pilar de la Puente & Abdel Kareem Azab

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Luderer, M.J., de la Puente, P. & Azab, A.K. Advancements in Tumor Targeting Strategies for Boron Neutron Capture Therapy. Pharm Res 32, 2824–2836 (2015). https://doi.org/10.1007/s11095-015-1718-y

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  • DOI: https://doi.org/10.1007/s11095-015-1718-y

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