Synthesis and in vitro evaluation of the phenylboric acid derivative entrapped lipiodol in boron neutron capture therapy for hepatoma.
BACKGROUND
Hepatoma, a common cancer in Taiwan, responds poorly to conventional therapies. Boron neutron capture therapy (BNCT) may provide a promising approach for hepatoma therapy. In this study, a pharmaceutical composition, phenylboric acid derivative entrapped lipiodol (PBAD-lipiodol), was synthesized and characterized. In vitro study was used for evaluation of PBAD-lipiodol for the BNCT of hepatoma.


METHODS
alpha Track observation was used to identify the boron compound in the TLC plate and to evidence the uniform distribution of boron in the PBAD-lipiodol. Inductively coupled plasma-atomic emission spectroscopy and neutron activation analysis were used to determine the concentrations of boron and lipiodol, respectively. Human hepatoma HepG2 cells were used for in vitro experiments. A Nomarski optical microscope was used to investigate the uptake of PBAD-lipiodol globules in individual hepatoma cells.


RESULTS
PBAD-lipiodol was stable in human serum. The boron source, PBAD, was uniformly distributed in PBAD-lipiodol. Many of the PBAD-lipiodol globules were internalized and retained in HepG2 cells, and the boron concentration of HepG2 cells reached 269 ppm after 72 hours of PBAD-lipiodol treatment.


CONCLUSIONS
In vitro studies revealed that PBAD-lipiodol could deliver a therapeutically effective amount of PBAD as a boron source for the BNCT of hepatoma. PBAD-lipiodol is a potential new boron drug for the BNCT of hepatoma.
Chou
Fong-In
FI
Nuclear Science and Technology, Development Center, National Tsing Hua University, Hsinchu, Taiwan 300, Republic of China. fichou@mx.nthu.edu.tw
Chung
Hsiao-Ping
HP
Shieh
Ming-Shueh
MS
Huang
Ching-Wen
CW
Chung
Ren-Jei
RJ
Liu
Hong-Ming
HM
Yang
Jeng-Yann
JY
Chi
Chin-Wen
CW
Lin
Yung-Chang
YC
Lui
Wing-Yiu
WY
Kai
Ji-Jung
JJ
D016754:Boron Neutron Capture Therapy / Q000379:methods*; D001897:Boronic Acids / Q000138:chemical synthesis* / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D003470:Culture Media; D004355:Drug Stability; D006801:Humans; D007459:Iodized Oil / Q000138:chemical synthesis* / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000097:blood / Q000532:radiotherapy*
D001897:Boronic Acids; D003470:Culture Media; D007459:Iodized Oil; C010686:benzeneboronic acid