TY - JOUR
T1 - A phase I study of SR-4554 via intravenous administration for noninvasive investigation of tumor hypoxia by magnetic resonance spectroscopy in patients with malignancy
AU - Seddon, B.M.
AU - Payne, G.S.
AU - Simmons, L.
AU - Ruddle, R.
AU - Grimshaw, R.
AU - Tan, S.
AU - Turner, A.
AU - Raynaud, F.
AU - Halbert, G.W.
AU - Leach, M.O.
AU - Judson, I.
AU - Workman, P.
PY - 2003
Y1 - 2003
N2 - 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.
AB - 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.
KW - cancer research
KW - clinical cancer research
KW - spectroscopy
KW - biomedical sciences
UR - http://clincancerres.aacrjournals.org/
UR - http://clincancerres.aacrjournals.org/cgi/content/abstract/9/14/5101
M3 - Article
SN - 1078-0432
VL - 9
SP - 5101
EP - 5112
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 14
ER -
