Applications of Nitroimidazole In Vivo Hypoxia Imaging in Ischemic Stroke

Abstract

Background and Purpose-Nitroimidazole imaging is a promising contender for noninvasive in vivo mapping of brain hypoxia after stroke. However, there is a dearth of knowledge about the behavior of these compounds in the various pathophysiologic situations encountered in ischemic stroke. In this article we report the findings from a systematic review of the literature on the use of the nitroimidazoles to map hypoxia after stroke. Summary of Review-We describe the characteristics of nitroimidazoles as imaging tracers, their pharmacology, and results of both animal and clinical studies during and after focal cerebral ischemia. Findings in brain tumors are also presented to the extent that they enlighten results in stroke. Early results from application of kinetic modeling for quantitative measurement of tracer binding are briefly discussed. Conclusions-Based on this literature review, nitroimidazole hypoxia imaging agents are of considerable interest in stroke because they appear, both in animal models and in humans, to specifically detect the severely hypoxic viable tissue, but not the reperfused nor the necrotic tissue. To fully realize this potential in stroke, however, formal validation by concurrent measurement of tissue oxygen tension, together with development of novel ligands with faster distribution kinetics, faster clearance from normal tissue, and well-defined trapping mechanisms, are important goals for future investigations.

Microneedle-array patches loaded with hypoxia-sensitive vesicles provide fast glucose-responsive insulin delivery

“…The incorporation of hydrophobic NI groups renders the derived HA amphiphilic, enabling the formation of GRVs in the aqueous solution (37,38). Moreover, NI provides an hypoxiasensitive element, which is expected to be bioreduced under hypoxic conditions (24,27). The reduced product with amine groups is water-soluble, leading to disassembly of GRVs.…”

“…To achieve hypoxia-responsive transduction, 2-nitroimidazole (NI), a hydrophobic component that has often been applied in cancer imaging due to its high sensitivity to the hypoxic condition in tumor sites, was used (24,25). NI can be converted to hydrophilic 2-aminoimidazoles under a hypoxic environment via a single-electron reduction catalyzed by a series of nitroreductases coupled to bioreducing agents, such as NADPH, a plentiful coenzyme in tissues (24)(25)(26)(27). We conjugated amine-functionalized NI with HA (molecular mass of 300 kDa), which is well known to have excellent biocompatibility and biodegradability (28)(29)(30).…”

Hemodynamic Factors and Perfusion Abnormalities in Early Neurological Deterioration

“…In one study that used positron emission tomography with 18 F-fluoromisonidazole, believed to map the hypoxic viable tissue but not the normally perfused or the already necrotic tissue, 55 increased likelihood of neurological deterioration occurred if a large proportion of the hypoxic tissue subsequently progressed to infarction. 56 However, concomitant perfusion studies were not reported, and to what degree the hypoxic tissue defined with 18 F-fluoromisonidazole represents only penumbra is still not clear.…”

Development of 68Ga-labeled multivalent nitroimidazole derivatives for hypoxia imaging

“…Radiolabeled nitroimidazole derivatives are used for imaging hypoxic tissue because the nitroimidazole residue is reduced to reactive chemical species that can bind to intracellular components in the absence of sufficient oxygen [1][2][3][4][5].…”