Boron Neutron Capture Therapy: Clinical Application and Research Progress

Cheng, Xiang; Li, Fanfan; Liu, Liang

doi:10.3390/curroncol29100622

Cited by 30 publications

(13 citation statements)

References 124 publications

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“… 106 Although preliminary clinical results of BNCT are promising, further research is needed in order to find more selective boron compounds. 107 …”

Section: Novel Lines Of Research In Glioblastoma and Gliomas In Generalmentioning

confidence: 99%

Recurrent Glioblastoma: Ongoing Clinical Challenges and Future Prospects

Pineda¹,

Doménech²,

Hernández³

et al. 2023

OTT

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Virtually all glioblastomas treated in the first-line setting will recur in a short period of time, and the search for alternative effective treatments has so far been unsuccessful. Various obstacles remain unresolved, and no effective salvage therapy for recurrent glioblastoma can be envisaged in the short term. One of the main impediments to progress is the low incidence of the disease itself in comparison with other pathologies, which will be made even lower by the recent WHO classification of gliomas, which includes molecular alterations. This new classification helps refine patient prognosis but does not clarify the most appropriate treatment. Other impediments are related to clinical trials: glioblastoma patients are often excluded from trials due to their advanced age and limiting neurological symptoms; there is also the question of how best to measure treatment efficacy, which conditions the design of trials and can affect the acceptance of results by oncologists and medicine agencies. Other obstacles are related to the drugs themselves: most treatments cannot cross the blood-brain-barrier or the brain-to-tumor barrier to reach therapeutic drug levels in the tumor without producing toxicity; the drugs under study may have adverse metabolic interactions with those required for symptom control; identifying the target of the drug can be a complex issue. Additionally, the optimal method of treatment – local vs systemic therapy, the choice of chemotherapy, irradiation, targeted therapy, immunotherapy, or a combination thereof – is not yet clear in glioblastoma in comparison with other cancers. Finally, in addition to curing or stabilizing the disease, glioblastoma therapy should aim at maintaining the neurological status of the patients to enable them to return to their previous lifestyle. Here we review currently available treatments, obstacles in the search for new treatments, and novel lines of research that show promise for the future.

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“… 106 Although preliminary clinical results of BNCT are promising, further research is needed in order to find more selective boron compounds. 107 …”

Section: Novel Lines Of Research In Glioblastoma and Gliomas In Generalmentioning

confidence: 99%

Recurrent Glioblastoma: Ongoing Clinical Challenges and Future Prospects

Pineda¹,

Doménech²,

Hernández³

et al. 2023

OTT

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“…Locher (1936) proposed the concept of neutron capture therapy in the mid‐1930s, but only after the end of the Second World War, the development of nuclear reactors for medicine allowed to start clinical trials of BNCT (Jin et al, 2022). Although the clinical trials showed the promising results, there is a number of limitations to the widespread use of BNCT technology (Cheng et al, 2022; Jin et al, 2022). Achieving optimal boron concentrations in tumor cells, normal tissue, and blood is the most important problem in the BNCT (Cheng et al, 2022; Sauerwein et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

“…Although the clinical trials showed the promising results, there is a number of limitations to the widespread use of BNCT technology (Cheng et al, 2022; Jin et al, 2022). Achieving optimal boron concentrations in tumor cells, normal tissue, and blood is the most important problem in the BNCT (Cheng et al, 2022; Sauerwein et al, 2021). Currently, despite the development of new targeted boron delivery drugs, only second‐generation boron drugs, such as boronophenylalanine and sodium borocaptate, are being used in clinical trials (Barth et al, 2018; Dymova et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Lithium salts cytotoxicity and accumulation in melanoma cells in vitro

Taskaeva,

Kasatova,

Razumov

et al. 2023

J of Applied Toxicology

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Boron neutron capture therapy is a perspective selective technology for the destruction of cancer cells, while the use of lithium instead of boron may represent a new and promising vector for the development of neutron capture therapy (NCT). The aim of the study was a comparative assessment of the cytotoxicity of various lithium salts, as well as an analysis of the accumulation of lithium in tumor cells in vitro to determine the possibility of using lithium in NCT. The cytotoxicity of lithium salts was determined using MTT‐test and colony forming assay on human fibroblasts BJ‐5ta, human skin melanoma SK‐Mel‐28, and mouse skin melanoma B16 cell lines. An assessment of lithium concentration in cells was performed using inductively coupled plasma atomic emission spectrometry. Our results showed that three different lithium salts at a concentration of 40 μg/ml are not toxic for both tumor and normal cells. The highest uptake values were obtained on murine melanoma B16 cells when exposed to lithium carbonate (0.8 μg/106 cells); however, human melanoma SK‐Mel‐28 cells effectively accumulated both lithium carbonate and lithium citrate (about 0.46 μg/106 cells for two salts). Thus, our results demonstrate a range of non‐toxic doses of lithium salts and a high uptake of lithium by tumor cells, which indicates the possibility to use the lithium in NCT.

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“…In particu-lar, glioblastoma is an aggressive malignant brain tumor, characterized by rapid and invasive growth that remains almost incurable. To date, there have been a number of examples of the successful use of BNCT for the treatment of brain tumors in clinics [2][3][4].…”

Section: Introductionmentioning

confidence: 99%

“…However, none of them has yet been approved for clinical applications. The only boron-containing drugs now used for BNCT in clinics are based on boronophenylalanine (such as Steboronine ® from Stella Pharma [8]) or sodium borocaptate [2]. These compounds cannot be precisely addressed to the tumor, and their pharmacokinetics and biodistribution are not optimal, so their tumor uptake is characterized by significant variability [9].…”

Section: Introductionmentioning

confidence: 99%

Aptamers for Addressed Boron Delivery in BNCT: Effect of Boron Cluster Attachment Site on Functional Activity

Новопашина

Дымова

Davydova

et al. 2022

IJMS

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Among the great variety of anti-cancer therapeutic strategies, boron neutron capture therapy (BNCT) represents a unique approach that doubles the targeting accuracy due to the precise positioning of a neutron beam and the addressed delivery of boron compounds. We have recently demonstrated the principal possibility of using a cell-specific 2′-F-RNA aptamer for the targeted delivery of boron clusters for BNCT. In the present study, we evaluated the amount of boron-loaded aptamer inside the cell via two independent methods: quantitative real-time polymerase chain reaction and inductive coupled plasma–atomic emission spectrometry. Both assays showed that the internalized boron level inside the cell exceeds 1 × 109 atoms/cell. We have synthesized closo-dodecaborate conjugates of 2′-F-RNA aptamers GL44 and Waz, with boron clusters attached either at the 3′- or at the 5′-end. The influence of cluster localization was evaluated in BNCT experiments on U-87 MG human glioblastoma cells and normal fibroblasts and subsequent analyses of cell viability via real-time cell monitoring and clonogenic assay. Both conjugates of GL44 aptamer provided a specific decrease in cell viability, while only the 3′-conjugate of the Waz aptamer showed the same effect. Thus, an individual adjustment of boron cluster localization is required for each aptamer. The efficacy of boron-loaded 2′-F-RNA conjugates was comparable to that of 10B-boronophenylalanine, so this type of boron delivery agent has good potential for BNCT due to such benefits as precise targeting, low toxicity and the possibility to use boron clusters made of natural, unenriched boron.

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Boron Neutron Capture Therapy: Clinical Application and Research Progress

Cited by 30 publications

References 124 publications

Recurrent Glioblastoma: Ongoing Clinical Challenges and Future Prospects

Recurrent Glioblastoma: Ongoing Clinical Challenges and Future Prospects

Lithium salts cytotoxicity and accumulation in melanoma cells in vitro

Aptamers for Addressed Boron Delivery in BNCT: Effect of Boron Cluster Attachment Site on Functional Activity

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