Synthesis and preliminary in vivo toxicity evaluation of an iodinated sulfidoborate.

摘要

An iodine-labeled (sup 10)B-carrier would enable the biodistribution of (sup 10)B to be imaged noninvasively in patients so as to optimize the timing of neutron exposure for BNCT. While Na(sub 2)B(sub l2)H(sub 11)SH (BSH) is in clinical use for BNCT in Japan, its disulfido dimer Na(sub 4)B(sub 24)H(sub 22)S(sub 2) (BSSB) is also under consideration. We describe the synthesis of an iodinated product of the dimer for possible use in BNCT and compare its toxicity in normal mice to that of BSSB. Periodination of BSSB can be carried out under reaction conditions similar to those used for B(sub 12)H(sup 12)(sup (minus)2). We surmise from this preliminary in vivo experiment that IBSSB may be slightly hepatotoxic to mice. Since the putative weight ratio of iodine to boron-10 in IBSSB is 11.5, the presence of a therapeutically adequate concentration of (sup 10)B in tumor, for example 30 (mu)g (sup 10)B per gram tumor, would be associated with 345 (mu)g I per gram tumor. This would be suitable for imaging a tumor in the brain and for quantifying the iodine using computed tomography (CT) without using conventional contrast enhancement. (sup 10)B concentrations useful for BNCT of malignant gliomas should be readily quantified by conventional CT using (sup 10)B-IBSSB as a combined radiographic contrast agent and (sup 10)B-carrier. Alternatively, iodine-radiolabeled IBSSB would allow visualization and quantification of iodine in the tumor by single photon emission computed tomography (SPECT). Because boron and iodine are linked covalently in IBSSB, quantification of iodine in the tumor would thereby also quantify boron in the tumor noninvasively using either radiolabeled or nonradiolabeled IBSSB in SPECT or CT, respectively, provided that in vivo deiodination of IBSSB is sufficiently slow.