Introduction: Benzotriazine-1,4-dioxides (BTDOs) such as tirapazamine (TPZ) and\nits derivatives act as radiosensitizers of hypoxic tissues. The benzotriazine-1-monoxide\n(BTMO) metabolite (SR 4317, TPZMO) of TPZ also has radiosensitizing properties, and via\nunknown mechanisms, is a potent enhancer of the radiosensitizing effects of TPZ. Unlike their\n2-nitroimidazole radiosensitizer counterparts, radiolabeled benzotriazine oxides have not been\nused as radiopharmaceuticals for diagnostic imaging or molecular radiotherapy (MRT) of hypoxia.\nThe radioiodination chemistry for preparing model radioiodinated BTDOs and BTMOs is now\nreported. Hypothesis: Radioiodinated 3-(2-iodoethoxyethyl)-amino-1,2,4- benzotriazine-1,4-dioxide\n(I-EOE-TPZ), a novel bioisosteric analogue of TPZ, and 3-(2-iodoethoxyethyl)-amino-1,2,4-\nbenzotriazine-1-oxide (I-EOE-TPZMO), its monoxide analogue, are candidates for in vivo and in vitro\ninvestigations of biochemical mechanisms in pathologies that develop hypoxic microenvironments.\nIn theory, both radiotracers can be prepared from the same precursors. Methods: Radioiodination\nprocedures were based on classical nucleophilic [131I]iodide substitution on Tos-EOE-TPZ (P1) and by\n[131I]iodide exchange on I-EOE-TPZ (P2). Reaction parameters, including temperature, reaction time,\nsolvent and the influence of pivalic acid on productsâ?? formation and the corresponding radiochemical\nyields (RCY) were investigated. Results: The [131I]iodide labeling reactions invariably led to the\nsynthesis of both products, but with careful manipulation of conditions the preferred product could\nbe recovered as the major product. Radioiodide exchange on P2 in ACN.........
Loading....