The Anti-Proliferative Effect of Boron Neutron Capture Therapy in a Prostate Cancer Xenograft Model.
OBJECTIVE
Boron neutron capture therapy (BNCT) is a selective radiation treatment for tumors that preferentially accumulate drugs carrying the stable boron isotope, 10B. BNCT has been evaluated clinically as an alternative to conventional radiation therapy for the treatment of brain tumors, and more recently, recurrent advanced head and neck cancer. Here we investigated the effect of BNCT on prostate cancer (PCa) using an in vivo mouse xenograft model that we have developed.


METHODS
Mice bearing the xenotransplanted androgen-independent human PCa cell line, PC3, were divided into four groups: Group 1: untreated controls; Group 2: Boronophenylalanine (BPA); Group 3: neutron; Group 4: BPA-mediated BNCT. We compared xenograft growth among these groups, and the body weight and any motility disturbance were recorded. Immunohistochemical (IHC) studies of the proliferation marker, Ki-67, and TUNEL staining were performed 9 weeks after treatment.


RESULTS
The in vivo studies demonstrated that BPA-mediated BNCT significantly delayed tumor growth in comparison with the other groups, without any severe adverse events. There was a significant difference in the rate of freedom from gait abnormalities between the BPA-mediated BNCT group and the other groups. The IHC studies revealed that BNCT treatment significantly reduced the number of Ki-67-positive cells in comparison with the controls (mean ± SD 6.9 ± 1.5 vs 12.7 ± 4.0, p<0.05), while there was no difference in the number of apoptotic cells, suggesting that BPA-mediated BNCT reduced PCa progression without affecting apoptosis at 9 weeks post-treatment.


CONCLUSIONS
This study has provided the first preclinical proof-of-principle data to indicate that BPA-mediated BNCT reduces the in vivo growth of PCa. Although further studies will be necessary, BNCT might be a novel potential treatment for PCa.
Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka, Japan.
Kiyoshi
K
Takahara
Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka, Japan.
Teruo
T
Inamoto
Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka, Japan.
Koichiro
K
Minami
Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka, Japan.
Yuki
Y
Yoshikawa
Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka, Japan.
Tomoaki
T
Takai
Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka, Japan.
Naokazu
N
Ibuki
Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka, Japan.
Hajime
H
Hirano
Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka, Japan.
Hayahito
H
Nomi
Department of Neurosurgery, Osaka Medical College, Osaka, Japan.
Shinji
S
Kawabata
Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka, Japan.
Satoshi
S
Kiyama
Department of Neurosurgery, Osaka Medical College, Osaka, Japan.
Shin-Ichi
S
Miyatake
Department of Neurosurgery, Osaka Medical College, Osaka, Japan.
Toshihiko
T
Kuroiwa
Radiation Oncology and Particle Radiation Oncology Research Center, Research Reactor Institute, Kyoto University, Sennan-gun, Osaka, Japan.
Minoru
M
Suzuki
Research Center of Boron Neutron Capture Therapy, Research Organization for the 21st Century, Osaka Prefecture University, Sakai, Japan.
Mitsunori
M
Kirihata
Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka, Japan.
Haruhito
H
Azuma
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D001896:Boron Compounds / Q000494:pharmacology*; D016754:Boron Neutron Capture Therapy / Q000379:methods; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects*; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009502:Neutrons / Q000627:therapeutic use*; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D023041:Xenograft Model Antitumor Assays / Q000379:methods
C436045:4-dihydroxyborylphenylalanine; D001896:Boron Compounds; D010649:Phenylalanine