Evaluation of the Key Advantages between Two Modalities of Boronophenylalanine Administration for Clinical Boron Neutron Capture Therapy Using an Animal Model

Yu-Chuan Lin; Yi-Jang Lee; Yi-Wei Chen; Shan-Ying Wang; Fong-In Chou

doi:10.3390/cells11172736

Evaluation of the Key Advantages between Two Modalities of Boronophenylalanine Administration for Clinical Boron Neutron Capture Therapy Using an Animal Model

Cells. 2022 Sep 1;11(17):2736. doi: 10.3390/cells11172736.

Authors

Yu-Chuan Lin^{1

2}, Yi-Jang Lee², Yi-Wei Chen^{3

4

5}, Shan-Ying Wang^{2

6}, Fong-In Chou^{1

7}

Affiliations

¹ Nuclear Science and Technology Development Center, National Tsing Hua University, Hsinchu City 300044, Taiwan.
² Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei City 112304, Taiwan.
³ Department of Oncology, Taipei Veterans General Hospital, Taipei City 112201, Taiwan.
⁴ College of Medicine, National Yang Ming Chiao Tung University, Taipei City 112304, Taiwan.
⁵ Department of Medical Imaging and Radiological Technology, Yuanpei University of Medical Technology, Hsinchu City 300102, Taiwan.
⁶ Department of Nuclear Medicine, Far Eastern Memorial Hospital, New Taipei City 220216, Taiwan.
⁷ College of Nuclear Science, National Tsing Hua University, Hsinchu City 300044, Taiwan.

Abstract

In clinical boron neutron capture therapy (BNCT), boronophenylalanine (BPA) administrations through one-step infusion (OSI) and two-step infusion (TSI) are the most widely used. This study compared the advantages of OSI and TSI using a human oral squamous cell carcinoma-bearing animal model. OSI was administered at a high-dose rate of 20 mg/kg/min for 20 min (total dose: 400 mg/kg) as the first step infusion. TSI was a prolonged infusion at a low-dose rate of 1.67 mg/kg/min for 15, 30, 45, and 60 min (total dose: 25, 50, 75, and 100 mg/kg) following the first step infusion. The sigmoid E_max model was used to evaluate the boron accumulation effect in the tumor. The advantages of TSI were observed to be greater than those of OSI. The observed advantages of TSI were as follows: a stable level of boron concentration in blood; tumor to blood boron ratio (T/B); tumor to muscle boron ratio (T/M); and skin to blood boron ratio (S/B). The boron accumulation effect in tumors increased to 68.98%. Thus, effective boron concentration in these tumor cells was achieved to enhance the lethal damage in BNCT treatment. Boron concentration in the blood was equal to that in the skin. Therefore, the equivalent dose was accurately estimated for the skin.

Keywords: boron accumulation effect; boron concentration; boron neutron capture therapy; boron ratio; boronophenylalanine; one step infusion; pharmacodynamic; two step infusion.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Boron
Boron Compounds / therapeutic use
Boron Neutron Capture Therapy*
Brain Neoplasms* / drug therapy
Carcinoma, Squamous Cell* / drug therapy
Carcinoma, Squamous Cell* / radiotherapy
Disease Models, Animal
Humans
Mouth Neoplasms* / drug therapy
Phenylalanine / therapeutic use

Substances

Boron Compounds
Phenylalanine
Boron

Grants and funding

This research was funded by National Science and Technology Council of Taiwan (NSC 99-3111-B-007-001), National YangMing Chiao Tung University Far Eastern Memorial Hospital Joint Research Program of Taiwan (NYCU-FEMH 111DN05) and National Science and Technol-ogy Council of Taiwan (MOST 109-2314-B-010-021-MY3).