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Title: Characterization of fluoromisonidazole binding in stroke.
Austin Authors: Spratt, Neil J;Ackerman, Uwe;Tochon-Danguy, Henri J ;Donnan, Geoffrey A ;Howells, David William
Affiliation: Department of Medicine, University of Melbourne, and National Stroke Research Institute, Austin Health, Heidelberg, Victoria, Australia
Issue Date: 8-Jun-2006
Publication information: Stroke; A Journal of Cerebral Circulation 2006; 37(7): 1862-7
Abstract: [18F]fluoromisonidazole (FMISO) positron emission tomography has been used to image hypoxia early after human stroke. To further study the role of hypoxia in stroke and the binding characteristics of FMISO, we aimed to develop [3H]FMISO autoradiography in an animal stroke model. We hypothesized that [3H]FMISO binding is prolonged, allowing correlation with 24-hour histology, and that there is no FMISO binding after effective reperfusion.Temporary middle cerebral artery (MCA) occlusion was performed in rats, followed by [3H]FMISO administration. Tissue preparation for autoradiography and histology (from the same sections) was performed 2.5 hours after MCA occlusion (MCAo; replicating [18F]FMISO studies). Then, otherwise identical cohorts with tissue preparation at 2.5 or 24 hours were prepared. For reperfusion studies, animals had 1-hour MCAo, with [3H]FMISO administered 1 hour after reperfusion.[3H]FMISO autoradiography provided a high-resolution image of hypoxia throughout the ischemic territory. Delaying animal death from 2.5 to 24 hours allowed histological changes of stroke to develop, without significantly altering either relative intensity (1.88+/-0.06 and 2.02+/-0.11, respectively) or volume (25+/-6 mm3 and 28+/-5 mm3, respectively) of hypoxic binding. [3H]FMISO binding did not occur after effective reperfusion, despite histological injury from the preceding MCAo.[3H]FMISO autoradiography of hypoxia in experimental stroke offers several advantages. Bound FMISO is retained in tissues long term, enabling direct correlation with 24-hour histology. It is not bound after effective reperfusion. Therefore, positive [18F]FMISO positron emission tomography studies in stroke patients are indicative of ongoing tissue hypoxia, not merely recent tissue injury.
Gov't Doc #: 16763190
DOI: 10.1161/01.STR.0000226908.93295.9d
Journal: Stroke
Type: Journal Article
Subjects: Animals
Cell Hypoxia
Cerebrovascular Circulation
Contrast Media.pharmacokinetics
Fluorine Radioisotopes.pharmacokinetics
Hypoxia, Brain.etiology.pathology.radionuclide imaging
Infarction, Middle Cerebral Artery.complications.pathology.physiopathology.radionuclide imaging
Laser-Doppler Flowmetry
Misonidazole.analogs & derivatives.analysis.pharmacokinetics
Positron-Emission Tomography
Protein Binding
Radioactive Tracers
Rats, Sprague-Dawley
Time Factors
Appears in Collections:Journal articles

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