Boron Neutron Capture Therapy (BNCT) for Cutaneous Malignant Melanoma Using 10B-p-Boronophenylalanine (BPA) with Special Reference to the Radiobiological Basis and Clinical Results

Fukuda, Hiroshi

doi:10.3390/cells10112881

Cited by 29 publications

(29 citation statements)

References 45 publications

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“…Therefore, the first requirement for BNCT is the preferential and effective uptake of boron compounds in tumor cells. BPA has been clinically used for BNCT in the treatment of malignant melanoma ( 6 , 8 ), malignant brain tumors ( 10 , 23 ), recurrent head and neck cancer ( 11 , 12 , 24 ), and malignant mesothelioma ( 13 , 14 ). However, no literature was found to report the treatment of BPA for gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

“…In the clinical situation, Fukuda et al. reported a half-life of 48 min after infusion of BPA to human patients ( 6 , 25 ). These results implied that multiple doses or continuous infusions of BPA should be recommended to maintain the high and steady boron concentration in blood, subsequently pushing enough boron into tumor tissue.…”

Section: Discussionmentioning

confidence: 99%

“…In the clinical situation, Fukuda et al. reported that in patients with melanoma treated with BPA, the melanoma/blood ratio of boron ranged from 2.1 to 3.8 and the skin/blood ratio of boron was 1.31-0.22 ( 6 ).…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of Pharmacokinetics of Boronophenylalanine and Its Uptakes in Gastric Cancer

et al. 2022

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Boron neutron capture therapy (BNCT), a cellular-level particle radiation therapy, combines boron compounds selectively delivered to tumor tissue with neutron irradiation. Boronophenylalanine (BPA) is a boron compound widely used in malignant melanoma, malignant brain tumors, and recurrent head and neck cancer. However, neither basic nor clinical research was reported for the treatment of gastric cancer using BPA. Selective distribution of boron in tumors rather than that in blood or normal tissue prior to neutron irradiation is required for the successful treatment of BNCT. This study evaluated the pharmacokinetics and safety of 10B-labeled BPA (10B-BPA, abbreviated as BPA) and its uptakes in gastric cancer. Pharmacokinetics and safety were evaluated in Sprague–Dawley (SD) rats intravenously injected with BPA. The uptakes of boron in gastric cancer cell line MKN45 and in cell-derived xenografts (CDX) and patient-derived xenografts (PDX) animal models were measured. The results showed that the boron concentration in the blood of rats decreased fast in the first 30 min followed by a steady decrease following the observation time, having a half-life of 44.11 ± 8.90 min and an AUC-last of 815.05 ± 62.09 min×μg/ml. The distribution of boron in different tissues (heart, liver, lung, stomach, and small intestine) of rats revealed a similar pattern in blood except for that in the brain, kidney, and bladder. In MKN45 cells, boron concentration increased in a time- and concentration-dependent manner. In both CDX and PDX animal models, the boron is preferentially distributed in tumor tissue rather than in blood or normal tissues. In addition, BPA had no significant adverse effects in rats. Taken together, the results suggested that BPA revealed a fast decrease in boron concentration in rats and is more likely to distribute in tumor cells and tissue.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Evaluation of Pharmacokinetics of Boronophenylalanine and Its Uptakes in Gastric Cancer

et al. 2022

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“…Similarly, Mishima and colleagues successfully treated 22 patients with cutaneous melanoma with BNCT between the years of 1987 and 2002. This study reported a complete response rate of 68.2% and a partial response rate of 23% [ 2 , 4 , 5 ].…”

Section: Introduction To Bnctmentioning

confidence: 99%

Exploring the Biological and Physical Basis of Boron Neutron Capture Therapy (BNCT) as a Promising Treatment Frontier in Breast Cancer

Seneviratne

Advani

Trifiletti

et al. 2022

Cancers

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BNCT is a high LET radiation therapy modality that allows for biologically targeted radiation delivery to tumors while reducing normal tissue impacts. Although the clinical use of BNCT has largely been limited to phase I/II trials and has primarily focused on difficult-to-treat malignancies such as recurrent head and neck cancer and recurrent gliomas, recently there has been a renewed interest in expanding the use of BNCT to other disease sites, including breast cancer. Given its high LET characteristics, its biologically targeted and tumor specific nature, as well as its potential for use in complex treatment settings including reirradiation and widespread metastatic disease, BNCT offers several unique advantages over traditional external beam radiation therapy. The two main boron compounds investigated to date in BNCT clinical trials are BSH and BPA. Of these, BPA in particular shows promise in breast cancer given that is taken up by the LAT-1 amino acid transporter that is highly overexpressed in breast cancer cells. As the efficacy of BNCT is directly dependent on the extent of boron accumulation in tumors, extensive preclinical efforts to develop novel boron delivery agents have been undertaken in recent years. Preclinical studies have shown promise in antibody linked boron compounds targeting ER/HER2 receptors, boron encapsulating liposomes, and nanoparticle-based boron delivery systems. This review aims to summarize the physical and biological basis of BNCT, the preclinical and limited clinical data available to date, and discuss its potential to be utilized for the successful treatment of various breast cancer disease states.

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“…Currently, 10 B-4-borono-L-phenylalanine (L-BPA) and sodium borocaptate (BSH) are common boron delivery agents in clinical use [13], and the sources of thermal neutrons are mainly from nuclear reactors or acceleratorbased neutron sources [14,15]. Although BNCT is not been widely used in large-scale clinical trials, BNCT has recently achieved promising results in the treatment malignant brain tumors [16][17][18][19], recurrent head and neck cancer [20], and melanomas [21,22]. Even for recurrent glioblastoma and recurrent head and neck cancer, BNCT is comparable to other treatments, with a median survival of approximately 12 months [23].…”

Section: Introductionmentioning

confidence: 99%

Compassionate Treatment of Brainstem Tumors with Boron Neutron Capture Therapy: A Case Series

Chen

Lee

Lin

et al. 2022

Life

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Brainstem tumors are heterogenous and cancerous glioma tumors arising from the midbrain, pons, and the medulla that are relatively common in children, accounting for 10% to 20% of all pediatric brain tumors. However, the prognosis of aggressive brainstem gliomas remains extremely poor despite aggressive treatment with chemotherapy and radiotherapy. That means there are many life-threatening patients who have exhausted all available treatment options and are beginning to face end-of-life stage. Therefore, the unique properties of highly selective heavy particle irradiation with boron neutron capture therapy (BNCT) may be well suited to prolong the lives of patients with end-stage brainstem gliomas. Herein, we report a case series of life-threatening patients with end-stage brainstem glioma who eligible for Emergency and Compassionate Use, in whom we performed a scheduled two fractions of salvage BNCT strategy with low treatment dosage each time. No patients experienced acute or late adverse events related to BNCT. There were 3 patients who relapsed after two fractionated BNCT treatment, characterized by younger age, lower T/N ratio, and receiving lower treatment dose. Therefore, two fractionated low-dose BNCT may be a promising treatment for end-stage brainstem tumors. For younger patients with low T/N ratios, more fractionated low-dose BNCT should be considered.

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Boron Neutron Capture Therapy (BNCT) for Cutaneous Malignant Melanoma Using 10B-p-Boronophenylalanine (BPA) with Special Reference to the Radiobiological Basis and Clinical Results

Cited by 29 publications

References 45 publications

Evaluation of Pharmacokinetics of Boronophenylalanine and Its Uptakes in Gastric Cancer

Evaluation of Pharmacokinetics of Boronophenylalanine and Its Uptakes in Gastric Cancer

Exploring the Biological and Physical Basis of Boron Neutron Capture Therapy (BNCT) as a Promising Treatment Frontier in Breast Cancer

Compassionate Treatment of Brainstem Tumors with Boron Neutron Capture Therapy: A Case Series

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