Abstract
Boron neutron capture therapy (BNCT) is a targeted radiation therapy under clinical trial in Taiwan. Boron-10 delivered into the tumor cells disintegrates after capturing a neutron, and the high energy heavy charged particles produced from the nuclear event destroy cancer cells, with only marginal damage to the surrounding normal tissues. BNCT has been used in clinical trials to treat various types of cancers. In 2009, Prof. Fong-In Chou of National Tsing Hua University found, in addition to borophenylalanine (BPA) and borocaptate (BSH), boric acid (BA) could also be the boron carrier for BNCT. Specifically, boric acid could be a promising agent for BNCT treatment of hepatocellular carcinoma (HCC). However, the underlying mechanism that influence tumor to normal tissue (T/N) ratio of the BA uptake and the transport process is still unclear. There are numerous reports showing that tumor microenvironment is different from the surrounding normal cells, including the glycoprotein profile, glucose metabolism and microenvironment pH value. Other reports also show that BA could form complexes with carboxylates, which involve covalent interactions that are reversible in aqueous solution. For these reasons, we hypothesized the differences between tumor and normal cells microenvironment may cause differential uptake of boron/BA into the liver cancer cells prior neutron irradiation. Consequently, our experimental data implied glucose metabolic condition and acidic environment might regulate the uptake of boron/BA by the liver cancer cells. Meanwhile, in order to accelerate the preclinical study of BA-mediated BNCT in established a zebrafish xenograft model with mouse melanoma cell line B16-F10 and adapted a transgenic zebrafish line that could develop spontaneous melanoma. We demonstrated that zebrafish could absorb boron in the delivery form of BA by orbital injection. A holding device was developed to immobilize the zebrafish during neutron irradiation. This novel zebrafish BNCT platform shall help us to understand the BA-mediated BNCT mechanism and speed up its translational application in the future.