scholarly journals Aza-BODIPY: A New Vector for Enhanced Theranostic Boron Neutron Capture Therapy Applications

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1953
Author(s):  
Ghadir Kalot ◽  
Amélie Godard ◽  
Benoît Busser ◽  
Jacques Pliquett ◽  
Mans Broekgaarden ◽  
...  
Keyword(s):  
Boron Neutron Capture Therapy ◽  
Neutron Capture ◽  
Ex Vivo ◽  
Chorioallantoic Membrane ◽  
Water Soluble ◽  
Neutron Capture Therapy ◽  
Breakdown Spectroscopy ◽  
Boron Neutron Capture ◽  
Tumor Area ◽  
Slow Neutrons

Boron neutron capture therapy (BNCT) is a radiotherapeutic modality based on the nuclear capture of slow neutrons by stable 10B atoms followed by charged particle emission that inducing extensive damage on a very localized level (<10 μm). To be efficient, a sufficient amount of 10B should accumulate in the tumor area while being almost cleared from the normal surroundings. A water-soluble aza-boron-dipyrromethene dyes (BODIPY) fluorophore was reported to strongly accumulate in the tumor area with high and BNCT compatible Tumor/Healthy Tissue ratios. The clinically used 10B-BSH (sodium borocaptate) was coupled to the water-soluble aza-BODIPY platform for enhanced 10B-BSH tumor vectorization. We demonstrated a strong uptake of the compound in tumor cells and determined its biodistribution in mice-bearing tumors. A model of chorioallantoic membrane-bearing glioblastoma xenograft was developed to evidence the BNCT potential of such compound, by subjecting it to slow neutrons. We demonstrated the tumor accumulation of the compound in real-time using optical imaging and ex vivo using elemental imaging based on laser-induced breakdown spectroscopy. The tumor growth was significantly reduced as compared to BNCT with 10B-BSH. Altogether, the fluorescent aza-BODIPY/10B-BSH compound is able to vectorize and image the 10B-BSH in the tumor area, increasing its theranostic potential for efficient approach of BNCT.

scholarly journals Synthesis, Molecular Docking, and In Vitro Boron Neutron Capture Therapy Assay of Carboranyl Sinomenine

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4697
Author(s):  
Jianghong Cai ◽  
Narayan S. Hosmane ◽  
Masao Takagaki ◽  
Yinghuai Zhu
Keyword(s):  
Rheumatoid Arthritis ◽  
Molecular Docking ◽  
Boron Neutron Capture Therapy ◽  
Neutron Capture ◽  
Dimethyl Formamide ◽  
Neutron Capture Therapy ◽  
Boron Neutron Capture ◽  
Elemental Analyses ◽  
Slow Neutrons

In comparison with pristine sinomenine and carborane precursors, the calculations of molecular docking with matrix metalloproteinases (MMPs) and methylcarboranyl-n-butyl sinomenine showed improved interactions. Accordingly, methylcarboranyl-n-butyl sinomenine shows a high potential in the treatment of rheumatoid arthritis (RA) in the presence of slow neutrons. The reaction of potassium salt of sinomenie, which is generated from the deprotonation of sinomenine (1) using potassium carbonate in a solvent of N,N-dimethyl formamide, with 4-methylcarboranyl-n-butyl iodide, (2) forms methylcarboranyl-n-butyl sinomenine (3) in 54.3% yield as a new product. This new compound was characterized by 1H, 13C, and 11B NMR spectroscopy, FT-IR spectroscopy, and elemental analyses to confirm its molecular composition. In addition to molecular docking interactions with MMPs, the in vitro killing effects of 3, along with its toxicity measurements, exhibited its potential to be the new drug delivery agent for boron neutron capture synovectomy (BNCS) and boron neutron capture therapy (BNCT) for the treatment of rheumatoid arthritis (RA) and cancers in the presence of slow neutrons, respectively.

Distribution of 10B after Infusion of Na210B12H11SH into a Patient with Malignant Astrocytoma: Implications for Boron Neutron Capture Therapy

Neurosurgery ◽  
1989 ◽  
Vol 24 (1) ◽  
pp. 6-11 ◽  
Author(s):  
Gerald C. Finkel ◽  
Charles E. Poletti ◽  
Ralph G. Fairchild ◽  
Daniel N. Slatkin ◽  
William H. Sweet
Keyword(s):  
Brain Tumors ◽  
Boron Neutron Capture Therapy ◽  
Neutron Capture ◽  
Nuclear Reactor ◽  
Neutron Capture Therapy ◽  
Malignant Astrocytoma ◽  
Intraarterial Infusion ◽  
Tumor Bearing ◽  
Boron Neutron Capture ◽  
Slow Neutrons

Abstract If a sufficient concentration of the stable isotope 10B is introduced into a neoplasm, radiation therapy can be effected by short-range heavy charged particles from the disintegration of 10B by slow neutrons. Brain tumors were irradiated postoperatively by Hatanaka and co-workers in Japan using a 1 to 2 hour intraarterial infusion of 10B-enriched Na2B12H11SH (Na210B12H11SH) before exposure of the tumor-bearing area of the brain to slow neutrons from a 100 kilowatt nuclear reactor. The clinical outcome of such boron neutron capture therapy has been favorably impressive in some patients, but its efficacy in brain tumors needs improvement. In our study, a terminally ill patient with malignant astrocytoma was infused intravenously with Na210B12H11SH for 25 hours. The postmortem distribution of 10B in unfixed, frozen, tumor-bearing brain and spinal cord tissues was studied by comparing representative cryostat sections of these specimens with neutron-induced heavy charged particle radiographs of the same sections. Preferential accumulation of 10B was observed in the tumor, with relatively little accumulation of 10B in the parenchyma of the central nervous system.

scholarly journals Water-Soluble closo-Docecaborate-Containing Pteroyl Derivatives Targeting Folate Receptor-Positive Tumors for Boron Neutron Capture Therapy

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1615 ◽  
Author(s):  
Fumiko Nakagawa ◽  
Hidehisa Kawashima ◽  
Taiki Morita ◽  
Hiroyuki Nakamura
Keyword(s):  
Boron Neutron Capture Therapy ◽  
Neutron Capture ◽  
Human Cancer ◽  
Folate Receptor ◽  
Water Soluble ◽  
Cell Uptake ◽  
Neutron Capture Therapy ◽  
Human Cancer Cells ◽  
Boron Neutron Capture ◽  
Ic50 Values

Water-soluble pteroyl-closo-dodecaborate conjugates (PBCs 1–4), were developed as folate receptor (FRα) targeting boron carriers for boron neutron capture therapy (BNCT). PBCs 1–4 had adequately low cytotoxicity with IC50 values in the range of 1~3 mM toward selected human cancer cells, low enough to use as BNCT boron agents. PBCs 1–3 showed significant cell uptake by FRα positive cells, especially U87MG glioblastoma cells, although the accumulation of PBC 4 was low compared with PBCs 1–3 and L-4-boronophenylalanine (L-BPA). The cellular uptake of PBC 1 and PBC 3 by HeLa cells was arrested by increasing the concentration of folate in the medium, indicating that the major uptake mechanisms of PBC 1–3 are primarily through FRα receptor-mediated endocytosis.

A Novel Approach to the Syntheses of Functionalized, Water-Soluble Icosahedral Carboranyl Anions. Crystal Structure of Methyl N-[(Trimethylamineboryl)carbonyl]-L-tyrosinate: A Synthon for Novel Carboranylpeptides

2002 ◽  
Vol 67 (7) ◽  
pp. 1095-1108 ◽  
Author(s):  
Bernard F. Spielvogel ◽  
Geeta Rana ◽  
Kamesh Vyakaranam ◽  
Kurt Grelck ◽  
Kari E. Dicke ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Boron Neutron Capture Therapy ◽  
Neutron Capture ◽  
Water Soluble ◽  
Neutron Capture Therapy ◽  
Boron Neutron Capture ◽  
Novel Approach ◽  
Peptide Precursor

New functionalized water-soluble carboranyl anions have been prepared from ortho-carborane through lithiation and subsequent derivatization. The reaction of Li2[1,2-C2B10H10] with Me3NBH2X produced the carboranylborane dianions, [1,2-(BH2X)-1,2-C2B10H10]2- (X = H (2a), CN (2b), COOMe (2c), COOH (2d)), while the reaction of [1-R-2-Li-C2B10H10]- with Me3NBH2X produced the monoanions [1-R-2-BH2X-C2B10H10]- (R = C6H5, X = H (2e), CN (2f), COOH (2h), COOCH3 (2g), CONHCH(CH2OH)COOMe (2i), CONHCH(CHMe2)COOMe (2j), CONHCH(4-CH2C6H4OH)- COOMe (2k); R = Me, X = H (2l), COOH (2m)). These water-soluble carboranylboranes have the potential of being effective hydrophilic boron neutron capture therapy (BNCT) agents. The crystal structure of the peptide precursor Me3NBH2CONHCH(4-CH2C6H4OH)COOMe (3b) which showed a special promise as a BNCT agent is also described.

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

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.

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