Folate receptor-targeted novel boron compound for boron neutron capture therapy on F98 glioma-bearing rats
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Folic acid (FA) has high affinity for the folate receptor (FR), which is limited expressed in normal human tissues, but over-expressed in several tumor cells, including glioblastoma cells. In the present work, a novel pteroyl–closo-dodecaborate conjugate (PBC) was developed, in which the pteroyl group interacts with FR, and the efficacy of boron neutron capture therapy (BNCT) using PBC was investigated. Thus, in vitro and in vivo studies were performed using F98 rat glioma cells and F98 glioma-bearing rats. For the in vivo study, boronophenylalanine (BPA) was intravenously administered, while PBC was administered by convection-enhanced delivery (CED)—a method for direct local drug infusion into the brain of rats. Furthermore, a combination of PBC administered by CED and BPA administered by intravenous (i.v.) injection was also investigated. In the biodistribution experiment, PBC administration at 6 h after CED termination showed the highest cellular boron concentrations (64.6 ± 29.6 µg B/g). Median survival time (MST) of untreated controls was 23.0 days (range 21–24 days). MST of rats administered PBC (CED) followed by neutron irradiation was 31 days (range 26–36 days), which was similar to that of rats administered i.v. BPA (30 days; range 25–37 days). Moreover, the combination group [PBC (CED) and i.v. BPA] showed the longest MST (38 days; range 28–40 days). It is concluded that a significant MST increase was noted in the survival time of the combination group of PBC (CED) and i.v. BPA compared to that in the single-boron agent groups. These findings suggest that the combination use of PBC (CED) has additional effects.
KeywordsBoron neutron capture therapy Folic acid Folate receptor F98 glioma-bearing rat
This work was performed under the Research Program for Next Generation Young Scientists of “Dynamic Alliance for Open Innovation Bridging Human, Environment and Materials” in “Network Joint Research Center for Materials and Devices” with funds for T.K. supervised by H.N. The authors thank Dr. Barth (Department of Pathology, the Ohio State University, Columbus, OH, US) for providing the F98 rat glioma cells. The authors would like to thank Enago (http://www.enago.jp) for the English language review. This study was supported by Japan Society for the Promotion of Science (JSPS) KAKENHI Grant number JP17K10878 to S.K. [Grants-in-Aid for Scientific Research (C)] and Grant number JP17K16666 to R.H. [Grants-in-Aid for Young Scientists (B)].
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
Ethics approval and consent to participate
All procedures were performed in accordance with the guide for the care and use of laboratory animals as approved by the Animal Use Review Board and Ethical Committee of Osaka Medical College and Kyoto University Research Reactor Institute (KURRI; Kumatori, Osaka, Japan).
- Barth RF, Yang W, Huo T, Riley KJ, Binns PJ, Grecula JC, Gupta N, Rousseau J, Elleaume H (2011) Comparison of intracerebral delivery of carboplatin and photon irradiation with an optimized regimen for boron neutron capture therapy of the F98 rat glioma. Appl Radiat Isot 69(12):1813–1816CrossRefGoogle Scholar
- Coderre JA, Makar MS, Micca PL, Nawrocky MM, Liu HB, Joel DD, Slatkin DN, Amols HI (1993) Derivations of relative biological effectiveness for the high-let radiations produced during boron neutron capture irradiations of the 9L rat gliosarcoma in vitro and in vivo. Int J Radiat Oncol Biol Phys 27(5):1121–1129CrossRefGoogle Scholar
- Futamura G, Kawabata S, Nonoguchi N, Hiramatsu R, Toho T, Tanaka H, Masunaga SI, Hattori Y, Kirihata M, Ono K, Kuroiwa T, Miyatake SI (2017) Evaluation of a novel sodium borocaptate-containing unnatural amino acid as a boron delivery agent for neutron capture therapy of the F98 rat glioma. Radiat Oncol 12(1):26CrossRefGoogle Scholar
- Garin-Chesa P, Campbell I, Saigo PE, Lewis JL Jr, Old LJ, Rettig WJ (1993) Trophoblast and ovarian cancer antigen LK26. Sensitivity and specificity in immunopathology and molecular identification as a folate-binding protein. Am J Pathol 142(2):557–567Google Scholar
- Kunwar S, Chang S, Westphal M, Vogelbaum M, Sampson J, Barnett G, Shaffrey M, Ram Z, Piepmeier J, Prados M, Croteau D, Pedain C, Leland P, Husain SR, Joshi BH, Puri RK, Group PS (2010) Phase III randomized trial of CED of IL13-PE38QQR vs Gliadel wafers for recurrent glioblastoma. Neuro Oncol 12(8):871–881CrossRefGoogle Scholar
- Masunaga S, Sakurai Y, Tanaka H, Tano K, Suzuki M, Kondo N, Narabayashi M, Nakagawa Y, Watanabe T, Maruhashi A, Ono K (2014) The dependency of compound biological effectiveness factors on the type and the concentration of administered neutron capture agents in boron neutron capture therapy. SpringerPlus 3:128CrossRefGoogle Scholar
- Nakai KYT, Kumada H, Matsumura A (2014) Boron neutron capture therapy for glioblastoma A phase-I. II Clinical trial at JRR-4. Eur Assoc NeuroOncology 4(3):116–123Google Scholar
- Stevens PJ, Sekido M, Lee RJ (2004b) Synthesis and evaluation of a hematoporphyrin derivative in a folate receptor-targeted solid-lipid nanoparticle formulation. Anticancer Res 24(1):161–165Google Scholar
- Suzuki M, Kato I, Aihara T, Hiratsuka J, Yoshimura K, Niimi M, Kimura Y, Ariyoshi Y, Haginomori S, Sakurai Y, Kinashi Y, Masunaga S, Fukushima M, Ono K, Maruhashi A (2014) Boron neutron capture therapy outcomes for advanced or recurrent head and neck cancer. J Radiat Res 55(1):146–153CrossRefGoogle Scholar
- Weitman SD, Lark RH, Coney LR, Fort DW, Frasca V, Zurawski VR Jr, Kamen BA (1992a) Distribution of the folate receptor GP38 in normal and malignant cell lines and tissues. Cancer Res 52(12):3396–3401Google Scholar
- Weitman SD, Weinberg AG, Coney LR, Zurawski VR, Jennings DS, Kamen BA (1992b) Cellular localization of the folate receptor: potential role in drug toxicity and folate homeostasis. Cancer Res 52(23):6708–6711Google Scholar
- Yang W, Barth RF, Adams DM, Ciesielski MJ, Fenstermaker RA, Shukla S, Tjarks W, Caligiuri MA (2002) Convection-enhanced delivery of boronated epidermal growth factor for molecular targeting of EGF receptor-positive gliomas. Cancer Res 62(22):6552–6558Google Scholar
- Yang W, Barth RF, Wu G, Kawabata S, Sferra TJ, Bandyopadhyaya AK, Tjarks W, Ferketich AK, Moeschberger ML, Binns PJ, Riley KJ, Coderre JA, Ciesielski MJ, Fenstermaker RA, Wikstrand CJ (2006) Molecular targeting and treatment of EGFRvIII-positive gliomas using boronated monoclonal antibody L8A4. Clin Cancer Res 12(12):3792–3802CrossRefGoogle Scholar
- Yin D, Zhai Y, Gruber HE, Ibanez CE, Robbins JM, Kells AP, Kasahara N, Forsayeth J, Jolly DJ, Bankiewicz KS (2013) Convection-enhanced delivery improves distribution and efficacy of tumor-selective retroviral replicating vectors in a rodent brain tumor model. Cancer Gene Ther 20(6):336–341CrossRefGoogle Scholar