Clinical Viability of Boron Neutron Capture Therapy for Personalized Radiation Treatment

Abstract

Boron Neutron Capture Therapy (BNCT) is a promising binary disease-targeted therapy, as neutrons preferentially kill cells labeled with boron (10B), which makes it a precision medicine treatment modality that provides a therapeutic effect exclusively on patient-specific tumor spread. Contrary to what is usual in radiotherapy, BNCT proposes cell-tailored treatment planning rather than to the tumor mass. The success of BNCT depends mainly on the sufficient spatial biodistribution of 10B located around or within neoplastic cells to produce a high-dose gradient between the tumor and healthy tissue. However, it is not yet possible to precisely determine the concentration of 10B in a specific tissue in real-time using non-invasive methods. Critical issues remain to be resolved if BNCT is to become a valuable, minimally invasive, and efficient treatment. In addition, functional imaging technologies, such as PET, can be applied to determine biological information that can be used for the combined-modality radiotherapy protocol for each specific patient. Regardless, not only imaging methods but also proteomics and gene expression methods will facilitate BNCT becoming a modality of personalized medicine. This work provides an overview of the fundamental principles, recent advances, and future directions of BNCT as cell-targeted cancer therapy for personalized radiation treatment.

Tailored hyaluronic acid-based nanogels as theranostic boron delivery systems for boron neutron cancer therapy

“…Currently, two molecules are used in clinical trials for this purpose and are most of the time co-administered: namely BPA ( 10 B- p ‑boronophenylalanine, C 9 H 12 10 BNO 4 ) and BSH (sodium mercaptoundecahydro-closo-dodecaborate, Na 2 10 B 12 H 11 SH). BPA accumulates preferentially in the tumor with a Tumor/Surrounding tissue ratio > 2.5 (minimum ratio that should be reached for BNCT application), but the molecule contains only one boron atom ( Skwierawska et al, 2022 ). BSH clusters 12 boron atoms, but possesses a less favorable tumor accumulation ( Malouff et al, 2021 ; Sauerwein et al, 2012 ).…”

A Red-Emitting Fluorescence Sensor for Detecting Boronic Acid-Containing Agents in Cells

“…The nuclear reaction of the 10 B atoms determines the therapeutic effect of BNCT; therefore, quantifying the amount of 10B in the tumor cells and analyzing the intracellular localization are critical steps in developing BNCT agents [ 13 ]. Inductively coupled plasma optical emission spectrometry and inductively coupled plasma mass spectrometry are the most widely used methods for quantifying boron amounts in tissues and cells.…”

Organotrifluoroborate Sugar Conjugates for a Guided Boron Neutron Capture Therapy: From Synthesis to Positron Emission Tomography

“…To ensure the best therapeutic results, cancer irradiation should be performed when the concentration of the BNCT agent within the tumor is the highest possible, above 2 mM. , To date, three boron-containing molecules have been approved for clinical trials and one for clinical use in Japan (boronophenylalanine BPA–Steboronine, Stella Pharma Corporation, Chuo-ku, Osaka, Japan), but all of them are far from ideal, especially because they cannot be traced in vivo . As targeted therapy represents a major focus of biomedical research today, to guarantee further development for the BNCT approach, new boron-containing compounds should act as theranostic agents, both delivering the boron atom needed for the therapy and tracking the biodistribution of the molecule in real time. , …”

“…5 As targeted therapy represents a major focus of biomedical research today, to guarantee further development for the BNCT approach, new boron-containing compounds should act as theranostic agents, both delivering the boron atom needed for the therapy and tracking the biodistribution of the molecule in real time. 6,7 Boronated carbohydrate derivatives have received consideration in BNCT due to the preferential uptake of sugars by tumor cells, prompting us to design new BNCT theranostic agents based on monosaccharide scaffolds. 8−10 Recently, new boronic acid derivatives have been synthesized introducing a boronic acid moiety into the sugar skeleton.…”

“… 5 As targeted therapy represents a major focus of biomedical research today, to guarantee further development for the BNCT approach, new boron-containing compounds should act as theranostic agents, both delivering the boron atom needed for the therapy and tracking the biodistribution of the molecule in real time. 6 , 7 …”