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Strategies for Preclinical Studies Evaluating the Biological Effects of an Accelerator-based BNCT System

Kondo, Natsuko Masutani, Mitsuko Imamichi, Shoji Matsumoto, Yoshitaka Nakai, Kei 京都大学 DOI:10.1089/cbr.2022.0057

2023.04

概要

This review discusses the strategies of preclinical studies intended for accelerator-based (AB)-boron neutron capture therapy (BNCT) clinical trials, which were presented at the National Cancer Institute (NCI) Workshop on Neutron Capture Therapy held from April 20 to 22, 2022. Clinical studies of BNCT have been conducted worldwide using reactor neutron sources, with most targeting malignant brain tumors, melanoma, or head and neck cancer. Recently, small accelerator-based neutron sources that can be installed in hospitals have been developed. AB-BNCT clinical trials for recurrent malignant glioma, head and neck cancers, high-grade meningioma, melanoma, and angiosarcoma have all been conducted in Japan. The necessary methods, equipment, and facilities for preclinical studies to evaluate the biological effects of AB-BNCT systems in terms of safety and efficacy are described, with reference to two examples from Japan. The first is the National Cancer Center, which is equipped with a vertical downward neutron beam, and the other is the University of Tsukuba, which has a horizontal neutron beam. The preclinical studies discussed include cell-based assays to evaluate cytotoxicity and genotoxicity, in vivo cytotoxicity and efficacy of BNCT, and radioactivation measurements.

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Table 1. Current Status and Performance of Accelerators Intended for BNCT Clinical Trials

Institute

Kyoto

Accelerator type

University,

Target reaction

Cyclotron

Be(p,n)

Beam axis

Horizontal

Beam

Beam

energy

current

(MeV)

(mA)

30

Japan

Present status

Clinical trials for recurrent malignant glioma (MG)(JapicCTI-194742)19 and recurrent and

advanced head and neck (HN) cancer (JHN001)20 and preparing for basic research use

Kansai BNCT

Cyclotron

Be(p,n)

Horizontal

30

Research Center,

Clinical

trial

for

recurrent

MG

(JapicCTI-194742)19

and

Malignant

Meningioma

(jRCT2051190044) and treatments for recurrent and advanced HN cancers

Japan

Southern

Tohoku

Cyclotron

Be(p,n)

Horizontal

30

Hospital, Japan

National

Cancer

(JapicCTI-194640))21, JHN002 Look Up Study) and treatments for HN cancers

Electrodynamic

linear

Li(p,n)

Vertical

2.5

20

Clinical trial for Malignant Melanoma and angiosarcoma (JapicCTI-195062)22

linear

Be(p,n)

Horizontal

10

Preclinical

linear

Be(p,n)

Horizontal

10

Preclinical

Electrostatic accelerator

Li(p,n)

Horizontal

2.6

30

Commissioning

Electrostatic accelerator

Li(p,n)

Horizontal

2.5

10

Commissioning

Center, Tokyo

accelerator

Tsukuba University,

Electrodynamic

Japan

accelerator

Gachon

University

Gil Medical Center,

Clinical trials for MG (JapicCTI-194742)19 and recurrent and advanced HN cancer (JHN002

Electrodynamic

accelerator

South Korea

Helsinki University

Hospital, Finland

Xiamen

Humanity

Hospital, China

Table 2. The facilities of BNCT systems with vertical downward neutron-beam.

Facility

Beam port

Type of BNCT

Main neutron beam

system

Massachusetts Institute of

Downward

Technology Research

vertical &

Reactor (MITR) (USA)

horizontal

CICS-1 in National Cancer

Downward

Center (Japan)

vertical

Novosibirsk State University

Downward

(Ruccisa)

vertical

Reactor

Thermal neutron

AB-BNCT

Epithermal neutron

AB-BNCT

Epithermal neutron

...

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