Radiopharmaceuticals for hypoxic tissues

The authors have developed [F-18]fluoromisonidazole as a radiopharmaceutical for imaging very low O2 concentrations such as can be found in tumors. F-18 is made by the O-18(p,n) reaction in enriched water. The activity is azeotropically dried (MeCN) in the presence of [2.2.2] and K2CO3. Reaction with glycidyl tosylate yields volatile [F-18]epifluorohydrin which is distilled into a vessel and 2-nitroimidazole/KOH added. A 40% yield is achieved after 15 min at 115 degree C. The synthesis can be done with a robot in about 1.5 hrs, including preparative HPLC. The compound does not defluorinate in vivo. It is lipophilic and is sufficiently electron affinic to attract e- within cells engaged in e- transport (i.e. biochemically alive). The radical anion product can pass its e- to O2 (a futile cycle) or accept another e- and bind intracellularly via bioreductive alkylation. Biology experiments show that this tracer works by the same mechanism to identify hypoxia in tumors, stroke and acutely hypoxic myocardium. An advantage over [O-15] O2 is that pathology shows up as increased activity with the new tracer, decreased with O-15