Prospects for the new era of boron neutron capture therapy and subjects for the future

AbstractBoron Neutron Capture Therapy (BNCT) is facing a new era where different projects based on accelerators instead of reactors are under development. The new facilities can be placed at hospitals and will increase the number of clinical trials. The therapeutic effect of BNCT can be improved if a optimized epithermal neutron spectrum is obtained, for which the beam shape assembly is a key ingredient. In this paper we propose an optimal beam shaping assembly suited for an affordable low energy accelerator. The beam obtained with the device proposed accomplishes all the IAEA recommendations for proton energies between 2.0 and 2.1 MeV. In addition, there is an overall improvement of the figures of merit with respect to BNCT facilities and previous proposals of new accelerator-based facilities.

Download Full-text

In Vitro Studies to Define the Cell-Surface and Intracellular Targets of Polyarginine-Conjugated Sodium Borocaptate as a Potential Delivery Agent for Boron Neutron Capture Therapy

Cells ◽

10.3390/cells9102149 ◽

2020 ◽

Vol 9 (10) ◽

pp. 2149

Author(s):

Atsushi Fujimura ◽

Seiji Yasui ◽

Kazuyo Igawa ◽

Ai Ueda ◽

Kaori Watanabe ◽

...

Keyword(s):

Amino Acid ◽

Cell Surface ◽

Boron Neutron Capture Therapy ◽

Neutron Capture ◽

Cell Membrane Permeability ◽

Neutron Capture Therapy ◽

Translational Machinery ◽

Boron Neutron Capture ◽

The Future ◽

Intracellular Targets

Boron neutron capture therapy (BNCT) requires pharmaceutical innovations and molecular-based evidence of effectiveness to become a standard cancer therapeutic in the future. Recently, in Japan, 4-borono-L-phenylalanine (BPA) was approved as a boron agent for BNCT against head and neck (H&N) cancers. H&N cancer appears to be a suitable target for BPA-BNCT, because the expression levels of L-type amino acid transporter 1 (LAT1), one of the amino acid transporters responsible for BPA uptake, are elevated in most cases of H&N cancer. However, in other types of cancer including malignant brain tumors, LAT1 is not always highly expressed. To expand the possibility of BNCT for these cases, we previously developed poly-arginine peptide (polyR)-conjugated mercaptoundecahydrododecaborate (BSH). PolyR confers the cell membrane permeability and tumor selectivity of BSH. However, the molecular determinants for the properties are not fully understood. In this present study, we have identified the cluster of differentiation 44 (CD44) protein and translational machinery proteins as a major cell surface target and intracellular targets of BSH-polyR, respectively. CD44, also known as a stem cell-associated maker in various types of cancer, is required for the cellular uptake of polyR-conjugated molecules. We showed that BSH-polyR was predominantly delivered to a CD44High cell population of cancer cells. Once delivered, BSH-polyR interacted with the translational machinery components, including the initiation factors, termination factors, and poly(A)-biding protein (PABP). As a proof of principle, we performed BSH-polyR-based BNCT against glioma stem-like cells and revealed that BSH-polyR successfully induced BNCT-dependent cell death specifically in CD44High cells. Bioinformatics analysis indicated that BSH-polyR would be suitable for certain types of malignant tumors. Our results shed light on the biochemical properties of BSH-polyR, which may further contribute to the therapeutic optimization of BSH-BNCT in the future.

Download Full-text

Prof. Rolf F. Barth: the future of boron neutron capture therapy will depend on the clinical trials of accelerator-based boron neutron capture therapy

Therapeutic Radiology and Oncology ◽

10.21037/tro.2018.11.03 ◽

2018 ◽

Vol 2 ◽

pp. 58-58

Author(s):

Tan-Lun Yu

Keyword(s):

Clinical Trials ◽

Boron Neutron Capture Therapy ◽

Neutron Capture ◽

Neutron Capture Therapy ◽

Boron Neutron Capture ◽

The Future

Download Full-text

Boron Neutron Capture Therapy Using CICS-1 and SPM-011 for Malignant Melanoma and Angiosarcoma

Case Medical Research ◽

10.31525/ct1-nct04293289 ◽

2020 ◽

Author(s):

Keyword(s):

Malignant Melanoma ◽

Boron Neutron Capture Therapy ◽

Neutron Capture ◽

Neutron Capture Therapy ◽

Boron Neutron Capture

Download Full-text

HGG-05. REGRESSION OF RECURRENT GLIOBLASTOMA AFTER BORON NEUTRON CAPTURE THERAPY AND CHIMERIC ANTIGEN RECEPTOR T-CELL THERAPY IN A CHILD

Neuro-Oncology ◽

10.1093/neuonc/noaa222.296 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii345-iii345

Author(s):

Hsin-Hung Chen ◽

Yi-Wei Chen

Keyword(s):

T Cells ◽

T Cell ◽

Chimeric Antigen Receptor ◽

Boron Neutron Capture Therapy ◽

Neutron Capture ◽

Antigen Receptor ◽

Neutron Capture Therapy ◽

T Cell Therapy ◽

Boron Neutron Capture ◽

Car T

Abstract A 6 y/o girl with recurrent multifocal glioblastoma received 3 times of boron neutron capture therapy (BNCT) and chimeric antigen receptor (CAR)–engineered T cells targeting the tumor-associated antigen HER2. Multiple infusions of CAR T cells were administered over 30 days through intraventricular delivery routes. It was not associated with any toxic effects of grade 3 or higher. After BNCT and CAR T-cell treatment, regression of all existing intracranial lesions were observed, along with corresponding increases in levels of cytokines and immune cells in the cerebrospinal fluid, but new lesions recurred soon after the treatment. This clinical response continued for 14 months after the initiation of first recurrence.

Download Full-text