What dose of Hypoxyprobe -1 should be used for hypoxia marking experiments?
The extent of Hypoxprobe -1 binding in hypoxic tissue will depend on the rate of bioreductive activation and on tissue exposure to Hypoxprobe -1 (exposure index = concentration x time). It is hard to predict the rate of reductive metabolism but the effect of exposure can be examined. The calculation of Hypoxprobe -1 concentration is on the basis of pimonidazole hydrochloride (MW 290.7). Very good labeling is observed in spheroids exposed in vitro to 58mg/kg (concentration in medium) for 1 hour. The exposure index is 58mg/kg x 1 hour = 58mg/kg-hour. Very good labeling of tumor tissue and normal epithelia is obtained in humans with 0.5gm/m2 or ca 14mg/kg where the plasma half-life of Hypoxprobe -1 is 5 hours. The exposure index is 14 mg/kg x 5 hours = 70 mg/kg-hour. Very good labeling of tumor tissues in mice is obtained with 60 mg/kg where the half-life of Hypoxprobe -1 is 0.5 hours. The exposure index is 60mg/kg x 0.5 hours = 30 mg/kg – hour. In summary, for small animals of uniform si
