Synthesis of Borono Fluoro Deoxy D glucose as Boron carrier for Boron neutron capture therapy (BNCT)

Abstract

Objective: The 18F-labeled Deoxy-D-Glucose exhibits high affinity to cancer tissue as a PET (Positron Emission Tomography) imaging agent for metastatic cancers. Complexation of 10B to 18F-DG complex may create a useful BNCT (Boron Neutron Capture Therapy) agent for cancer therapy. In previous studies, complexation and characterization of 10B with DG were evaluated and biodistribution analysis was completed successfully. Radioactive tracer labeled 10B-DG will be a useful approach to uses for BNCT applications. Methods: The 18F-DG synthesized by ion exchange and complexed with 10B(OH)3 via pH reactions. 18F-DG-10B complexation was assayed with Agilent 1260 Infinity HPLC-DAD and Agilent 6420 Triple Quad LC/MS. Complexed molecule defragmented and fragmentation products assayed with Agilent 6420 Triple Quad LC/MS for confirmation. Results: 10B-18F-DG complex was obtained with ion-exchange pH reaction successfully. Complexation of two 10B(OH)3 to 18F-DG was determined with Triple Quad LC/MS. Purification of 10B-18F-DG is currently in progress. Conclusions: Radio-labelled 10B-DG will supply new insight to research for BNCT studies. Cancer detection and therapy will be applicable in the same schedule with 10B-18F-DG complex.

Keywords

• Boron Neutron Capture Therapy,Borono 2-Deoxy-D-glucose,Boronophenylalanine,Glucose,2-Fluoro-2-deoxy-D-glucose

Kaynakça

1. 1. Barth, R. F., Yang, W., Rotaru, J. H., Moeschberger, M. L., Boesel, C. P., Soloway, A. H., ... & Goodman, J. H. (2000). Boron neutron capture therapy of brain tumors: enhanced survival and cure following blood–brain barrier disruption and intracarotid injection of sodium borocaptate and boronophenylalanine. International Journal of Radiation Oncology* Biology* Physics, 47(1), 209-218.
2. 2. Barth, R. F., Vicente, M. H., Harling, O. K., Kiger, W. S., Riley, K. J., Binns, P. J., ... & Kawabata, S. (2012). Current status of boron neutron capture therapy of high grade gliomas and recurrent head and neck cancer. Radiation Oncology, 7(1), 146.
3. 3. Moss, R. L. (2014). Critical review, with an optimistic outlook, on Boron Neutron Capture Therapy (BNCT). Applied Radiation and Isotopes, 88, 2-11.
4. 4. Coderre, J. A., Elowitz, E. H., Chadha, M., Bergland, R., Capala, J., Joel, D. D., ... & Chanana, A. D. (1997). Boron neutron capture therapy for glioblastoma multiforme using p-boronophenylalanine and epithermal neutrons: Trial design and early clinical results. Journal of neuro-oncology, 33(1), 141-152.
5. 5. Aihara, T., Hiratsuka, J., Morita, N., Uno, M., Sakurai, Y., Maruhashi, A., ... & Harada, T. (2006). First clinical case of boron neutron capture therapy for head and neck malignancies using 18F‐BPA PET. Head & neck, 28(9), 850-855.
6. 6. Akan, Z., Demiroglu, H., Avcibasi, U., Oto, G., Ozdemir, H., Deniz, S., & Basak, A. S. (2014). Complexion of Boric Acid with 2-Deoxy-D-glucose (DG) as a novel boron carrier for BNCT. Medical Science and Discovery, 1(3), 65-71.
7. 7. Akan, Z., Ozdemir, H., Oto, G., Deniz, S., Kacar, O., Basak, A. S., ... & Demir, G. (2014). Genotoxicity and Cytotoxicity of novel 10B carrier ((2R)-4, 5, 6-trihydroxy-2-(hydroxymethyl) tetrahydro-2H-pyran-3-yl) boronic acid. Medical Science and Discovery, 1(4), 96-108.
8. 8. Akan, Z., Ozdemir, H., Oto, G., Uslu, H., Turkmen, M., & Yuksel, M. B. (2016). The treatment of metastatic prostate carcinoma with BNCT in the ITU TRIGA MARKII reactor on rat model.

9. 9. Miyatake, S. I., Kawabata, S., Yokoyama, K., Kuroiwa, T., Michiue, H., Sakurai, Y., ... & Ono, K. (2009). Survival benefit of boron neutron capture therapy for recurrent malignant gliomas. Journal of neuro-oncology, 91(2), 199.
10. 10. Pappin B, Kiefel MJ, Houston TA (2012). Boron-carbohydrate interactions. InCarbohydrates-Comprehensive Studies on Glycobiology and Glycotechnology. InTech.
11. 11. Böeseken J. (1913) On the storage of hydroxyl groups of polyoxide compounds in space. The configuration of saturated glycols and of alpha- and beta-glycose. Ber. Dtsch. Chem. Ges., 46: 2612–2628.