Abstract
Boron-neutron capture therapy (BNCT) is an attractive technique for cancer treatment. As such, α, α-cycloalkyl amino acids containing thiododecaborate ([B12H11]2−-S-) units were designed and synthesized as novel boron delivery agents for BNCT. In the present study, new thiododecaborate α, α-cycloalkyl amino acids were synthesized, and biological evaluation of the boron compounds as boron carrier for BNCT was carried out.
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Abbreviations
- BNCT:
-
Boron neutron capture therapy
- L-10BPA:
-
p-(10B)borono-l-phenylalanine
- 10BSH:
-
Mercapto-undeca-hydro-closo-dodeca(10B)borate
- ACBC:
-
1-Aminocyclo-butane-1-carboxylic acid
- PET:
-
Positron emission tomography
- ICP-OES:
-
Inductively coupled plasma optical emission spectrometry
- LAT:
-
L-type amino acid transporter
- EAATs:
-
Excitatory amino acid transporters
- ODS:
-
Octadecylsilyl
- WST:
-
Water soluble tetrazolium
- DMEM:
-
Dulbecco’s Modified Eagle’s Medium
- FBS:
-
Fetal bovine serum
- EDTA:
-
Ethylenediaminetetraacetic acid
- HEPES:
-
4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid
- PBS:
-
Phosphate-buffered saline
- NMR:
-
Nuclear magnetic resonance
- ESI–MS:
-
Electrospray ionization mass spectrometry
References
Barth RF, Coderre JA, Vicente MG, Blue TE (2005) Boron neutron capture therapy of cancer: current status and future prospects. Clin Canc Res 11:3987–4002
Gabel D, Moller D, Harfst S, Rosler J, Ketz H (1993) Synthesis of S-alkyl and S-acyl derivatives of mercaptoundeca-hydrododeca-borate, a possible boron carrier for neutron capture therapy. Inorg Chem 32:2276–2278
Guo H, Lai L, Butchbach ME, Lin CL (2002) Human glioma cells and undifferentiated primary astrocytes that express aberrant EAAT2 mRNA inhibit normal EAAT2 protein expression and prevent cell death. Mol Cell Neurosci 21:546–560
Hattori Y, Uehara K, Asano T, Tanimori S, Kirihata M (2010) Synthesis of new derivatives by hetero-Michael addition in water. Proceedings of 14th International Congress on Neutron Capture Therapy: 343–344
Hattori Y, Kusaka S, Mukumoto M, Uehara K, Asano T, Suzuki M, Masunaga S, Ono K, Tanimori S, Kirihata M (2012) Biological evaluation of dodecaborate-containing L-amino acids for boron neutron capture therapy. J Med Chem 55:6980–6984
Kanai Y, Segawa H, Miyamoto K, Uchino H, Takeda E, Endou H (1998) Expression cloning and characterization of a transporter for large neutral amino acids activated by heavy chain of 4F2 antigen (CD98). J Biol. Chem. 273:23629–23632
Kim DK, Kim IJ, Hwang S, Kook JH, Lee MC, Shin BA, Bae CS, Yoon JH, Ahn SG, Kim SA, Kanai Y, Endou H, Kim JK (2004) System L-amino acid transporters are differently expressed in rat astrocyte and C6 glioma cells. Neurosci Res 50:437–446
Kirihata M, Uehara K, Asano T (2007) Preparation of borocaptate (10B) (BSH) derivatives as hapten compound for production of antibody against BSH. WO2007097065, 30 Aug 2007
Kusaka S, Hattori Y, Uehara K, Asano T, Tanimori S, Kirihata M (2011) Synthesis of optically active dodecaborate-containing L-amino acids for BNCT. Appl Radiat Isot 69:1768–1770
Ogawa K, Wada H, Okada N, Harada I, Nakajima T, Pasquale BE, Tsuyama S (2005) EphB2 and ephrin-B1 expressed in the adult kidney regulate the cytoarchitecture of medullary tubule cells through Rho family GTPases. J Cell Sci 119:559–570
Oka S, Okudaira H, Yoshida Y, Schuster DM, Goodman MM, Shirakami Y (2012) Transport mechanisms of trans-1-amino-3-fluoro[1-(14)C]cyclobutanecarboxylic acid in prostate cancer cells. Nucl Med Biol 39:109–119
Rammeloo T, Stevens CV (2002) A new and short method for the synthesis of 2, 4-methanoproline. Chem. Commun. 3:250–251
Rice SL, Roney CA, Daumar P, Lewis JS (2011) The next generation of positron emission tomography radiopharmaceuticals in oncology. Semin Nucl Med 41:265–282
Soloshonok AV, Sorochinsky EA (2010) Practical methods for the synthesis of symmetrically α, α-disubstituted α-amino acids. Synthesis 14:2319–2344
Soloway AH, Tjarks W, Barnum BA, Rong FG, Barth RF, Codogni IM, Wilson JG (1998) The chemistry of neutron capture therapy. Chem Rev 98:1515–1562
Yoshimoto M, Kurihara H, Honda N, Kawai K, Ohe K, Fujii H, Itami J, Arai Y (2013) Predominant contribution of L-type amino acid transporter to 4-borono-2-18F-floro-phenylalanine uptake in human glioblastoma cells. Nucl Med Biol 40:625–629
Acknowledgments
This work was supported by the Adaptable and Seamless Technology Transfer Program through target-driven R&D, JST. We thank Professor K. Ogawa of Osaka Prefecture University for his technical support with immunostaining. We also thank Mr. H. Nakashima and Ms. Y. Ishino for the measurement of the ESI-MS.
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The authors have declared no conflict of interest.
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Hattori, Y., Kusaka, S., Mukumoto, M. et al. Synthesis and in vitro evaluation of thiododecaborated α, α- cycloalkylamino acids for the treatment of malignant brain tumors by boron neutron capture therapy. Amino Acids 46, 2715–2720 (2014). https://doi.org/10.1007/s00726-014-1829-5
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DOI: https://doi.org/10.1007/s00726-014-1829-5