Selective Melanoma Thermal Neutron Capture Therapy for Lymph Node Metastases

Mishima, Yutaka; Honda, C.; Ichihashi, M.; Shiono, M.; Wadabayashi, N.; Obara, Hideki; Hoshino, Junichi; Fukuda, Hiroshi; Karashima, Hiroshi; Kanda, Keiji; Kobayashi, Tooru; Yoshino, Kazuo

doi:10.1007/978-1-4615-2978-1_140

Cited by 7 publications

(2 citation statements)

References 2 publications

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“…10,13,14 Boronated tyrosine derivative 4-boronophenylalanine (BPA) is the most widely used boron delivery agent in the clinical setting. 15,16 However, inadequate tumor specificity has been a long-standing problem since the first application of BPA in 1987. 7,17 Besides the deficient uptake into the tumor tissue, another possible issue could be the metabolic instability of BPA, 18 as many shreds of evidence suggested that low concentration (μM) of H 2 O 2 could rapidly compromise the structure of phenylboronic acid 19−22 (Scheme S1 in Supporting Information).…”

Section: ■ Introductionmentioning

confidence: 99%

A Metabolically Stable Boron-Derived Tyrosine Serves as a Theranostic Agent for Positron Emission Tomography Guided Boron Neutron Capture Therapy

Shi

Zhang³

et al. 2019

Bioconjugate Chem.

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Boronophenylalanine (BPA) is the dominant boron delivery agent for boron neutron capture therapy (BNCT), and [18F]FBPA has been developed to assist the treatment planning for BPA-BNCT. However, the clinical application of BNCT has been limited by its inadequate tumor specificity due to the metabolic instability. In addition, the distinctive molecular structures between [18F]FBPA and BPA can be of concern as [18F]FBPA cannot quantitate boron concentration of BPA in a real-time manner. In this study, a metabolically stable boron-derived tyrosine (denoted as fluoroboronotyrosine, FBY) was developed as a theranostic agent for both boron delivery and cancer diagnosis, leading to PET imaging-guided BNCT of cancer. [18F]FBY was synthesized in high radiochemical yield (50%) and high radiochemical purity (98%). FBY showed high similarity with natural tyrosine. As shown in in vitro assays, the uptake of FBY in murine melanoma B16-F10 cells was L-type amino acid transporter (LAT-1) dependent and reached up to 128 μg/106 cells. FBY displayed high stability in PBS solution. [18F]FBY PET showed up to 6 %ID/g in B16-F10 tumor and notably low normal tissue uptake (tumor/muscle = 3.16 ± 0.48; tumor/blood = 3.13 ± 0.50; tumor/brain = 14.25 ± 1.54). Moreover, administration of [18F]FBY tracer along with a therapeutic dose of FBY showed high accumulation in B16-F10 tumor and low normal tissue uptake. Correlation between PET-image and boron biodistribution was established, indicating the possibility of estimating boron concentration via a noninvasive approach. At last, with thermal neutron irradiation, B16-F10 tumor-bearing mice injected with FBY showed significantly prolonged median survival without exhibiting obvious systemic toxicity. In conclusion, FBY holds great potential as an efficient theranostic agent for imaging-guided BNCT by offering a possible solution of measuring local boron concentration through PET imaging.

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Section: ■ Introductionmentioning

confidence: 99%

A Metabolically Stable Boron-Derived Tyrosine Serves as a Theranostic Agent for Positron Emission Tomography Guided Boron Neutron Capture Therapy

Shi

Zhang³

et al. 2019

Bioconjugate Chem.

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“…1 Additional potential applications of the BNCT concept include treatment of peripheral and intracranial metastatic melanomas, as well as rheumatoid arthritis. 2,3 BNCT research in the United States and Europe is concentrated on the use of epithermal neutron beams. An epithermal beam produces a peak in the thermal neutron flux, and hence boron neutron capture rate, at a distance several centimeters below the skin surface.…”

Section: Introductionmentioning

confidence: 99%

A Monte Carlo dosimetry‐based evaluation of the reaction near threshold for accelerator boron neutron capture therapy

et al. 2000

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Advanced methods of boron neutron capture therapy (BNCT) use an epithermal neutron beam in conjunction with tumor-targeting boron compounds for irradiation of glioblastomas and metastatic melanomas. A common neutron-producing reaction considered for accelerator-based BNCT is 7Li(p,n)7Be, whose cross section increases very rapidly within several tens of keV of the reaction threshold at 1.88 MeV. Operation in the proton energy region near threshold will have an appreciable thick target neutron yield, but the neutrons produced will have relatively low energies that require little moderation to reach the epithermal range desirable for BNCT. Because of its relatively low projected accelerator cost and the portability of the neutron source/target assembly, BNCT based on the near-threshold technique is considered an attractive candidate for widespread hospital use. A systematic Monte Carlo N-Particle (MCNP) investigation of the dosimetric properties of near-threshold neutron beams has been performed. Results of these studies indicate that accelerator proton energies between 1.93 and 1.99 MeV, using 5 cm of H2O moderator followed by thin 6Li and Pb shields, can provide therapeutically useful beams with treatment times less than one hour and accelerator currents less than 5 mA.

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Sodium Borocaptate and Boronopheynlalanine Alone or in Combination as Capture Agents for BNCT of the F98 Rat Glioma

Barth¹,

Rotaru²,

Staubus³

et al. 1996

Cancer Neutron Capture Therapy

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Selective Melanoma Thermal Neutron Capture Therapy for Lymph Node Metastases

Cited by 7 publications

References 2 publications

A Metabolically Stable Boron-Derived Tyrosine Serves as a Theranostic Agent for Positron Emission Tomography Guided Boron Neutron Capture Therapy

A Metabolically Stable Boron-Derived Tyrosine Serves as a Theranostic Agent for Positron Emission Tomography Guided Boron Neutron Capture Therapy

A Monte Carlo dosimetry‐based evaluation of the reaction near threshold for accelerator boron neutron capture therapy

Sodium Borocaptate and Boronopheynlalanine Alone or in Combination as Capture Agents for BNCT of the F98 Rat Glioma

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