The Anti-Proliferative Effect of Boron Neutron Capture Therapy in Prostate Cancer Xenograft Model

Journal Reference

PLoS One. 2015;10(9):e0136981.

Takahara K¹, Inamoto T¹, Minami K¹, Yoshikawa Y¹, Takai T¹, Ibuki N¹, Hirano H¹, Nomi H¹, Kawabata S², Kiyama S¹, Miyatake S², Kuroiwa T², Suzuki M³,Kirihata M⁴, Azuma H¹.

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1. Department of Urology, Faculty of Medicine, Osaka Medical College, Osaka, Japan.
2. Department of Neurosurgery, Osaka Medical College, Osaka, Japan.
3. Radiation Oncology and Particle Radiation Oncology Research Center, Research Reactor Institute, Kyoto University, Sennan-gun, Osaka, Japan.
4. Research Center of Boron Neutron Capture Therapy, Research Organization for the 21st Century, Osaka Prefecture University, Sakai, Japan.

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Abstract

PURPOSE:

Boron neutron capture therapy (BNCT) is a selective radiation treatment for tumors that preferentially accumulate drugs carrying the stable boron isotope, 10B. Boron neutron capture therapy 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 Boron neutron capture therapy on prostate cancer (PCa) using an in vivo mouse xenograft model that we have developed.

MATERIALS AND 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 Boron neutron capture therapy. 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 Boron neutron capture therapy 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 Boron neutron capture therapy 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 Boron neutron capture therapy 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 Boron neutron capture therapy reduces the in vivo growth of PCa. Although further studies will be necessary, Boron neutron capture therapy might be a novel potential treatment for PCa.

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