Development of an in vivo 19F magnetic resonance method for measuring oxygen deficiency in tumors

Abstract

A 19F magnetic resonance spectroscopy (MRS) approach to measuring hypoxia in experimental tumors in rats at a field strength of 2.35 T has been investigated in a combined study of in situ and excised tumors. The detection of tumor hypoxia is based on the hypoxia marker approach which depends on the selective, covalent binding of a fluorinated 2-nitroimidazole to hypoxic cells. The 19F MRS measurement of in vivo hypoxia marker binding was made at a fixed postinjection time when unbound, circulating marker molecule concentrations had dropped below detectable levels. A correlation between 19F MRS and scintillation counting measures of tumor-bound, tritium-labeled hypoxia marker was observed. There was no correlation between integrated 19F MRS hypoxia marker signals and the in vivo 31P MRS parameters of hypoxia which have been developed to measure normal tissue ischemia. Radiolabeling studies and previous immunohistochemical studies with the fluorinated hypoxia marker support the conclusion that the 19F MRS approach has promise as a physically noninvasive guide to the use of hypoxia-dependent therapies at clinically usable MRS field strengths.