Suppression of Tumor Growth in a Rabbit Hepatic Cancer Model by Boron Neutron Capture Therapy With Liposomal Boron Delivery Systems
Hironobu Yanagië, Masashi Yanagawa, Yasuyuki Morishita, Atsuko Shinohara, Novriana Dewi, Yasumasa Nonaka, Yoshitaka Furuya, Ryouji Mizumachi, YUUJI MURATA, Hiroyuki Nakamura, Minoru Suzuki, Yoshinori Sakurai, Hiroki Tanaka, Shin‐ichiro Masunaga, Koji Ono, Takumichi Sugihara, Masayuki Nashimoto, Haruo Yamauchi, Minoru Ōno, Jun Nakajima, Hiroyuki Takahashi
Abstract
Background/Aim: Tumor cell destruction by boron neutron capture therapy (BNCT) is attributed to the nuclear reaction between <sup>10</sup>B and thermal neutrons. The accumulation of <sup>10</sup>B atoms in tumor cells without affecting adjacent healthy cells is crucial for effective BNCT. We previously reported that several types of liposomal boron delivery systems (BDS) delivered effective numbers of boron atoms to cancer tissues, and showed tumor-growth suppression after thermal neutron irradiation. In the present study, we examined the effects of BNCT after intra-arterial infusion of <sup>10</sup>B-borono-dodecaborate (<sup>10</sup>BSH) by liposomal BDS in rabbit hepatic cancer models. Materials and Methods: We prepared <sup>10</sup>BSH-entrapped transferrin-conjugated polyethylene glycol liposomes constructed with distearoyl-boron lipid (TF-PEG-DSBL), and performed thermal neutron irradiation at the Kyoto University Institute for Integrated Radiation and Nuclear Science after intra-arterial infusion into rabbit VX-2 hepatic tumors. Results: Concentrations of <sup>10</sup>B in VX-2 tumors on delivery with TF-PEG-DSBL liposomes reached 25 ppm on day 3 after the injection. Tumor growth was suppressed by thermal neutron irradiation after intra-arterial injection of this <sup>10</sup>BSH-containing liposomal BDS, without damage to normal cells. Conclusion: The present results demonstrate the applicability of <sup>10</sup>B-containing TF-PEG-DSBL liposomes as a novel intra-arterial boron carrier in BNCT for cancer.