BNCT Pancreatic Cancer Treatment Strategy with Glucose- Conjugated Boron Drug

52 Pages Posted: 15 Mar 2024

See all articles by Takuya Fujimoto

Takuya Fujimoto

Okayama University

Fuminori Teraishi

Okayama University

Noriyuki Kanehira

Okayama University

Tomoyuki Tajima

Okayama University

Yoshinori Sakurai

Kyoto University - Particle Radiation Oncology Research Center

Natsuko Kondo

Kyoto University

Masahiro Yamagami

Okayama University

Atsushi Kuwada

Okayama University

Akira Morihara

Okayama University

Mizuki Kitamatsu

Kindai University

Atsushi Fujimura

Okayama University

Minoru Suzuki

Kyoto University

Yutaka Takaguchi

University of Toyama

Kunitoshi Shigeyasu

Okayama University

Toshiyoshi Fujiwara

Okayama University

Hiroyuki Michiue

Okayama University

Abstract

Multidisciplinary therapy centered on radical surgery for resectable pancreatic cancer is expected to prolong prognosis, but relies on CA19-9 biomarker levels to determine treatment strategy. Boron neutron capture therapy (BNCT) is a chemoradiotherapy using tumor hyperaccumulator boron drugs and neutron irradiation. The purpose of this study is to investigate novel boron drug agents for BNCT for pancreatic cancer. Bioinformatics was used to evaluate the uptake of current boron amino acid (BPA) drugs for BNCT into pancreatic cancer. The expression of the amino acid transporterLAT11, a BPA uptake transporter, was low in pancreatic cancer and even lower in high CA19-9 pancreatic cancer. In contrast, the glucose transporter was high in high CA19-9 pancreatic cancers and inversely correlated with LAT1 expression. Considering the low EPR effect in pancreatic cancer, we synthesized a small molecule Glucose-BSH, which is boron BSH bound to glucose, and confirmed its specific uptake in pancreatic cancer. uptake of Glucose-BSH was confirmed in an environment compatible with the tumor microenvironment. The therapeutic efficacy and safety of Glucose-BSH by therapeutic neutron irradiation were confirmed with BNCT. We report Glucose-BSH boron drug discovery study of a Precision Medicine BNCT with application to high CA19-9 pancreatic cancer.

Note:
Funding declaration: This work was supported by a Grant-in-aid for Takeda Science Foundation (2016049889) and JSPS KAKENHI (JP18K07324, JP19K09122, JP21K09176, JP22K08803, JP22K07639).

Conflict of Interests: All authors have no conflict of interest in this project.

Ethical Approval: All animal use and care procedures were conducted in accordance with ARRIVE 2.0 guidelines, approved by the Department of Animal Resources, Advanced Science Research Center, Okayama University (OKU-2020533, 2020706, 2021548) and the Kyoto University Institute for Integrated Radiation and Nuclear Science (KURNS) ethics committee (KURNS approval number 2021-38, 2022-38) and followed all required protocols.

Keywords: Boron neutron capture therapy (BNCT)high CA19-9 pancreatic cancerboron agentprecision BNCTglucose- conjugated medicinechemoradiation therapy

Suggested Citation

Fujimoto, Takuya and Teraishi, Fuminori and Kanehira, Noriyuki and Tajima, Tomoyuki and Sakurai, Yoshinori and Kondo, Natsuko and Yamagami, Masahiro and Kuwada, Atsushi and Morihara, Akira and Kitamatsu, Mizuki and Fujimura, Atsushi and Suzuki, Minoru and Takaguchi, Yutaka and Shigeyasu, Kunitoshi and Fujiwara, Toshiyoshi and Michiue, Hiroyuki, BNCT Pancreatic Cancer Treatment Strategy with Glucose- Conjugated Boron Drug. Available at SSRN: https://ssrn.com/abstract=4754039 or http://dx.doi.org/10.2139/ssrn.4754039

Takuya Fujimoto

Okayama University ( email )

1-1-1 Tsushimanaka, Kita Ward
Okayama, 700-0082
Japan

Fuminori Teraishi

Okayama University ( email )

1-1-1 Tsushimanaka, Kita Ward
Okayama, 700-0082
Japan

Noriyuki Kanehira

Okayama University ( email )

1-1-1 Tsushimanaka, Kita Ward
Okayama, 700-0082
Japan

Tomoyuki Tajima

Okayama University ( email )

1-1-1 Tsushimanaka, Kita Ward
Okayama, 700-0082
Japan

Yoshinori Sakurai

Kyoto University - Particle Radiation Oncology Research Center ( email )

Natsuko Kondo

Kyoto University ( email )

Yoshida-Honmachi
Sakyo-ku
Kyoto, 606-8501
Japan

Masahiro Yamagami

Okayama University ( email )

1-1-1 Tsushimanaka, Kita Ward
Okayama, 700-0082
Japan

Atsushi Kuwada

Okayama University ( email )

1-1-1 Tsushimanaka, Kita Ward
Okayama, 700-0082
Japan

Akira Morihara

Okayama University ( email )

1-1-1 Tsushimanaka, Kita Ward
Okayama, 700-0082
Japan

Mizuki Kitamatsu

Kindai University ( email )

Higashiosaka, Osaka
Japan

Atsushi Fujimura

Okayama University ( email )

1-1-1 Tsushimanaka, Kita Ward
Okayama, 700-0082
Japan

Minoru Suzuki

Kyoto University ( email )

Yoshida-Honmachi
Sakyo-ku
Kyoto, 606-8501
Japan

Yutaka Takaguchi

University of Toyama ( email )

Kunitoshi Shigeyasu

Okayama University ( email )

1-1-1 Tsushimanaka, Kita Ward
Okayama, 700-0082
Japan

Toshiyoshi Fujiwara

Okayama University ( email )

1-1-1 Tsushimanaka, Kita Ward
Okayama, 700-0082
Japan

Hiroyuki Michiue (Contact Author)

Okayama University ( email )

1-1-1 Tsushimanaka, Kita Ward
Okayama, 700-0082
Japan

Do you have a job opening that you would like to promote on SSRN?

Paper statistics

Downloads
48
Abstract Views
118
PlumX Metrics