Multi-Targeted Neutron Capture Therapy Combined with an 18 kDa Translocator Protein-Targeted Boron Compound Is an Effective Strategy in a Rat Brain Tumor Model.

Kashiwagi, Hideki; Hattori, Yoshihide; Kawabata, Shinji; Kayama, Ryo; Yoshimura, Kohei; Fukuo, Yusuke; Kanemitsu, Takuya; Shiba, Hiroyuki; Hiramatsu, Ryo; Takami, Toshihiro; Takata, Takushi; Tanaka, Hiroki; Watanabe, Tsubasa; Suzuki, Minoru; Hu, Naonori; Miyatake, Shin-Ichi; Kirihata, Mitsunori; Wanibuchi, Masahiko

Kashiwagi, Hideki; Hattori, Yoshihide; Kawabata, Shinji; Kayama, Ryo; Yoshimura, Kohei; Fukuo, Yusuke; Kanemitsu, Takuya; Shiba, Hiroyuki; Hiramatsu, Ryo; Takami, Toshihiro; Takata, Takushi; Tanaka, Hiroki; Watanabe, Tsubasa; Suzuki, Minoru; Hu, Naonori; Miyatake, Shin-Ichi; Kirihata, Mitsunori; Wanibuchi, Masahiko.

Afiliação

Kashiwagi H; Department of Neurosurgery, Osaka Medical and Pharmaceutical University, Osaka 569-8686, Japan.
Hattori Y; Research Center of BNCT, Osaka Metropolitan University, Osaka 599-8531, Japan.
Kawabata S; Department of Neurosurgery, Osaka Medical and Pharmaceutical University, Osaka 569-8686, Japan.
Kayama R; Department of Neurosurgery, Osaka Medical and Pharmaceutical University, Osaka 569-8686, Japan.
Yoshimura K; Department of Neurosurgery, Osaka Medical and Pharmaceutical University, Osaka 569-8686, Japan.
Fukuo Y; Department of Neurosurgery, Osaka Medical and Pharmaceutical University, Osaka 569-8686, Japan.
Kanemitsu T; Department of Neurosurgery, Osaka Medical and Pharmaceutical University, Osaka 569-8686, Japan.
Shiba H; Department of Neurosurgery, Osaka Medical and Pharmaceutical University, Osaka 569-8686, Japan.
Hiramatsu R; Department of Neurosurgery, Osaka Medical and Pharmaceutical University, Osaka 569-8686, Japan.
Takami T; Department of Neurosurgery, Osaka Medical and Pharmaceutical University, Osaka 569-8686, Japan.
Takata T; Institute for Integrated Radiation and Nuclear Science, Kyoto University, Osaka 590-0494, Japan.
Tanaka H; Institute for Integrated Radiation and Nuclear Science, Kyoto University, Osaka 590-0494, Japan.
Watanabe T; Institute for Integrated Radiation and Nuclear Science, Kyoto University, Osaka 590-0494, Japan.
Suzuki M; Institute for Integrated Radiation and Nuclear Science, Kyoto University, Osaka 590-0494, Japan.
Hu N; Kansai BNCT Medical Center, Osaka Medical and Pharmaceutical University, Osaka 569-8686, Japan.
Miyatake SI; Kansai BNCT Medical Center, Osaka Medical and Pharmaceutical University, Osaka 569-8686, Japan.
Kirihata M; Research Center of BNCT, Osaka Metropolitan University, Osaka 599-8531, Japan.
Wanibuchi M; Department of Neurosurgery, Osaka Medical and Pharmaceutical University, Osaka 569-8686, Japan.

Cancers (Basel) ; 15(4)2023 Feb 06.

Article em En | MEDLINE | ID: mdl-36831378

ABSTRACT

ABSTRACT

BACKGROUND:

Boron neutron capture therapy (BNCT) has been adapted to high-grade gliomas (HG); however, some gliomas are refractory to BNCT using boronophenylalanine (BPA). In this study, the feasibility of BNCT targeting the 18 kDa translocator protein (TSPO) expressed in glioblastoma and surrounding environmental cells was investigated.

METHODS:

Three rat glioma cell lines, an F98 rat glioma bearing brain tumor model, DPA-BSTPG which is a boron-10 compound targeting TSPO, BPA, and sodium borocaptate (BSH) were used. TSPO expression was evaluated in the F98 rat glioma model. Boron uptake was assessed in three rat glioma cell lines and in the F98 rat glioma model. In vitro and in vivo neutron irradiation experiments were performed.

RESULTS:

DPA-BSTPG was efficiently taken up in vitro. The brain tumor has 16-fold higher TSPO expressions than its brain tissue. The compound biological effectiveness value of DPA-BSTPG was 8.43 to F98 rat glioma cells. The boron concentration in the tumor using DPA-BSTPG convection-enhanced delivery (CED) administration was approximately twice as high as using BPA intravenous administration. BNCT using DPA-BSTPG has significant efficacy over the untreated group. BNCT using a combination of BPA and DPA-BSTPG gained significantly longer survival times than using BPA alone.