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ID: <

10670/1.vc5k49

>

·

DOI: <

10.26226/morressier.5cb72191ae0a0900158309e9

>

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Folate-Modified Cyclodextrin Improved The Active Tumor Accumulation And Therapeutic Effect Of BNCT Using BSH

Abstract

The therapeutic effect of boron neutron capture therapy (BNCT) greatly depends on the boron accumulation into the tumor, but the accumulation of existing compounds is limited. In this study, folic acid-modified cyclodextrin (ND201) purified with folate receptor (FR) was used to examine the improvement of specific and active accumulation of boron compounds on tumors. Colon-26 (FR+) and A549 (FR-) cells were inoculated to the behind of right legs of mice. The BSH mixed with ND201 was subcutaneously injected to the back of the neck of the mice. Boron concentration in the tumor cells was measured with ICPS-8100 (Shimadzu Corporation). The stability constant (Kc) and the stoichiometric ratio of BSH/ND201 complex (ND-BSH) were 1.4u00d710^4 (/M) and 0.5, respectively. It was found that ND- BSH stably binds in the blood, and the mixing ratio of 1: 1 is most efficient. ND-BSH showed high boron concentration (38.5 ppm) compared with BSH alone (11.25 ppm) for Colon-26 (FR+) tumors. The maximum tumor/blood ratio (T/B ratio) by ND-BSH was too high (6.58) compared with BSH alone (1.04) for Colon-26 (FR+) tumors. On the other hands, T/B ratio was similar between ND-BSH and BSH for A549 (FR-) tumors. After neutron irradiation, ND-BSH showed significant tumor suppressing effect compared with BSH alone (only for Colon-26 tumor). It was suggested that the usefulness of BSH-ND201 depends on the expression of folate receptor and chemical modification targeting folate receptor to existing boron compounds may contribute to improvement of therapeutic effect of BNCT.

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