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A phase I study of SR-4554 via intravenous administration for noninvasive investigation of tumor hypoxia by magnetic resonance spectroscopy in patients with malignancy

Seddon, B.M. and Payne, G.S. and Simmons, L. and Ruddle, R. and Grimshaw, R. and Tan, S. and Turner, A. and Raynaud, F. and Halbert, G.W. and Leach, M.O. and Judson, I. and Workman, P. (2003) A phase I study of SR-4554 via intravenous administration for noninvasive investigation of tumor hypoxia by magnetic resonance spectroscopy in patients with malignancy. Clinical Cancer Research, 9 (14). pp. 5101-12. ISSN 1557-3265

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Abstract

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.

Item type: Article
ID code: 5483
Keywords: cancer research, clinical cancer research, spectroscopy, biomedical sciences, Pharmacy and materia medica, Neoplasms. Tumors. Oncology (including Cancer), Cancer Research, Oncology
Subjects: Medicine > Pharmacy and materia medica
Medicine > Internal medicine > Neoplasms. Tumors. Oncology (including Cancer)
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Related URLs:
Depositing user: Strathprints Administrator
Date Deposited: 27 Feb 2008
Last modified: 04 Sep 2014 15:32
URI: http://strathprints.strath.ac.uk/id/eprint/5483

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