A Phase I study of SR-4554, a fluorinated 2-nitroimidazole noninvasive probe of tumor hypoxia detected by 19F magnetic resonance spectroscopy (MRS). Eight patients underwent pharmacokinetic studies, receiving doses of SR-4554 of 400-1600 mg/m2. Peak plasma concentrations increased linearly with the SR-4554 dose (r2 = 0.80; P = 0.0002). The plasma elimination half-life was relatively short (mean ± SD, 3.28 ± 0.59 h), and plasma clearance was quite rapid (mean ± SD, 12.8 ± 3.3 liters/h). Urinary recovery was generally high. SR-4554 was well tolerated. A single patient experienced dose-limiting toxicity (nausea and vomiting) at 1600 mg/m2. The maximum tolerated dose was 1400 mg/m2. SR-4554 was detected spectroscopically in tumors immediately after infusion at doses of 400-1600 mg/m2. At the highest dose (1600 mg/m2), SR-4554 was detectable in tumor at 8 h, but not at 27 h.
|Number of pages||5089|
|Journal||Clinical Cancer Research|
|Publication status||Published - 2003|
- cancer research
- clinical cancer research
- biomedical sciences