Clinical implementation of 4-dihydroxyborylphenylalanine synthesised by an asymmetric pathway

Kulvik, Martti; Vähätalo, Jyrki; Buchar, E.; Färkkilä, Markus; Järviluoma, Eija; Jääskeläinen, Juha E.; Křı́ž, Otomar; Laakso, Juha; Rasilainen, Merja; Ruókonen, Inkeri; Kallio, Merja

doi:10.1016/s0928-0987(02)00256-7

Cited by 14 publications

(7 citation statements)

References 28 publications

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“…BPA-F infusion. BPA was purchased from Katchem Ltd. (Kulvik et al, 2003). The BPA-F solution was prepared in the hospital pharmacy of HUCH, Helsinki.…”

Section: Methodsmentioning

confidence: 99%

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Biodistribution of boron after intravenous 4-dihydroxyborylphenylalanine-fructose (BPA-F) infusion in meningioma and schwannoma patients: A feasibility study for boron neutron capture therapy

Kulvik

Kallio

Laakso

et al. 2015

Applied Radiation and Isotopes

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We studied the uptake of boron after 100 mg/kg BPA infusion in three meningioma and five schwannoma patients as a pre-BNCT feasibility study. With average tumour-to-whole blood boron concentrations of 2.5, we discuss why BNCT could, and probably should, be developed to treat severe forms of the studied tumours. However, analysing 72 tumour and 250 blood samples yielded another finding: the plasma-to-whole blood boron concentrations varied with time, suggesting that the assumed constant boron ratio of 1:1 between normal brain tissue and whole blood deserves re-assessment.

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“…BPA-F infusion. BPA was purchased from Katchem Ltd. (Kulvik et al, 2003). The BPA-F solution was prepared in the hospital pharmacy of HUCH, Helsinki.…”

Section: Methodsmentioning

confidence: 99%

“…The solution was prepared at a concentration of 30 g/l (0.14 M) by combining BPA with a 10% molar excess of fructose in sterile water. The detailed procedure was previously described (Kulvik et al, 2003). The solution was intravenously administered via an IVAC™ infusion pump using Optiva 2™ or Venflon Insyte vein cannulas.…”

Section: Methodsmentioning

confidence: 99%

Biodistribution of boron after intravenous 4-dihydroxyborylphenylalanine-fructose (BPA-F) infusion in meningioma and schwannoma patients: A feasibility study for boron neutron capture therapy

Kulvik

Kallio

Laakso

et al. 2015

Applied Radiation and Isotopes

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“…First, 4-dihydroxyborylphenylalanine‒fructose complex (BPA–F) was prepared according to the literature (Fig. 1 C) 18 . Briefly, BPA (120 mg, 0.61 mmol) was mixed with MilliQ water (2 mL) in a round bottom flask at room temperature.…”

Section: Methodsmentioning

confidence: 99%

In vivo evaluation of the effects of combined boron and gadolinium neutron capture therapy in mouse models

Lee

Kim

Lim

et al. 2022

Sci Rep

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While boron neutron capture therapy (BNCT) depends primarily on the short flight range of the alpha particles emitted by the boron neutron capture reaction, gadolinium neutron capture therapy (GdNCT) mainly relies on gamma rays and Auger electrons released by the gadolinium neutron capture reaction. BNCT and GdNCT can be complementary in tumor therapy. Here, we studied the combined effects of BNCT and GdNCT when boron and gadolinium compounds were co-injected, followed by thermal neutron irradiation, and compared these effects with those of the single therapies. In cytotoxicity studies, some additive effects (32‒43%) were observed when CT26 cells were treated with both boron- and gadolinium-encapsulated PEGylated liposomes (B- and Gd-liposomes) compared to the single treatments. The tumor-suppressive effect was greater when BNCT was followed by GdNCT at an interval of 10 days rather than vice versa. However, tumor suppression with co-injection of B- and Gd-liposomes into tumor-bearing mice followed by neutron beam irradiation was comparable to that observed with Gd-liposome-only treatment but lower than B-liposome-only injection. No additive effect was observed with the combination of BNCT and GdNCT, which could be due to the shielding effect of gadolinium against thermal neutrons because of its overwhelmingly large thermal neutron cross section.

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“…Light yellow solid (0.093 mg, 70%). 1 (10) Under an argon atmosphere, methyl 2-acetamidoacrylate (0.06 g, 0.4 mmol) and 2 H 2 O (5 mL) were added to a solution of 7 (0.1 g, 0.4 mmol) in toluene (15 mL); the resulting two-phase system was vigorously stirred under reflux for 30 h. Purification was held in the same manner as for compound 8. Light yellow solid (90 mg, 66%).…”

Section: Generalmentioning

confidence: 99%

“…Radiation therapy has a central role in the management of malignant brain tumors, especially for the most aggressive ones [2][3][4]. First introduced in 1936 by Locher [5], the Boron Neutron Capture Therapy model (BNCT) is a promising type of radiation therapy for cancer that has the potential to be an important treatment for numerous types of tumors, including for those lying in areas that are difficult to access for surgery intervention, such as high-grade gliomas and metastatic brain tumors [6][7][8] Currently, only two low molecular weight boron-containing compounds, sodium mercapto-undecahydro-closo-dodecaborate (BSH, developed in about 1965) and a water-soluble fructose complex of borylphenylalanine (BPA, discovered in 1958), have been approved and found clinical use in BNCT [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

“Free of Base” Sulfa-Michael Addition for Novel o-Carboranyl-DL-Cysteine Synthesis

et al. 2020

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The sulfa-Michael addition reaction was applied for the two-step synthesis of o-carboranyl cysteine 1-HOOCCH(NH2)CH2S-1,2-C2B10H11 from the trimethylammonium salt of 1-mercapto-o-carborane and methyl 2-acetamidoacrylate. To avoid the decapitation of o-carborane into its nido-form, the “free of base” method under mild conditions in a system of two immiscible solvents toluene-H2O was developed. The replacement of H2O by 2H2O resulted in carboranyl-cysteine containing a deuterium label at the α-position of the amino acid 1-HOOCCD(NH2)CH2S-1,2-C2B10H11. The structure of the protected o-carboranyl cysteine was determined by single-crystal X-ray diffraction. The obtained compounds can be considered as potential agents for the Boron Neutron Capture Therapy of cancer.

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Clinical implementation of 4-dihydroxyborylphenylalanine synthesised by an asymmetric pathway

Cited by 14 publications

References 28 publications

Biodistribution of boron after intravenous 4-dihydroxyborylphenylalanine-fructose (BPA-F) infusion in meningioma and schwannoma patients: A feasibility study for boron neutron capture therapy

Biodistribution of boron after intravenous 4-dihydroxyborylphenylalanine-fructose (BPA-F) infusion in meningioma and schwannoma patients: A feasibility study for boron neutron capture therapy

In vivo evaluation of the effects of combined boron and gadolinium neutron capture therapy in mouse models

“Free of Base” Sulfa-Michael Addition for Novel o-Carboranyl-DL-Cysteine Synthesis

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