Abstract
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Objectives: In ischemic stroke, an imaging method to directly visualize the salvageable part of the affected brain would potentially improve therapy stratification and monitoring. In this study we preclinically tested [18F]fluoroetanidazole ([18F]FETA), a newer hypoxia PET marker, for its suitability in this regard.
Methods: Corticoencephalic rat cells were ex vivo exposed to nitrogen or air. pO2 was measured in the cell suspensions using an oxygen probe. Tracer cell uptake was determined up to 2h. Further, tracer biodistribution was determined in Sprague Dawley rats up to 3h after permanent middle cerebral artery occlusion (pMCAO) by gamma counting of organ radioactivity and by brain slice autoradiography.
Results: In vitro, the pO2 was <1 mmHg or ~70 mmHg under nitrogen or air. As compared to air, under nitrogen there was a time-dependent tracer uptake increase by the cells (2.0- and 2.8-fold at 1 and 2h, p<0.05). The biodistribution studies showed a fast blood clearance (0.7±0.2, 0.5±0.1, 0.3±0.03 and 0.2±0.03%ID/g at 15, 30, 60 and 120min p.i.), a rapid urinary excretion and a constantly low uptake in unaffected brain (0.1±0.02%ID/g). First brain autoradiographies 1h after pMCAO revealed a relevant [18F]FETA uptake in the ipsilateral MCA territory (2.0-fold as compared to reference region).
Conclusions: These results point to a potential of [18F]FETA to serve as a brain hypoxia marker for PET imaging. Its further evaluation in a large animal stroke model is therefore warranted.
Research Support: Supported by BMBF (PtJ-Bio 0313909).
- Society of Nuclear Medicine, Inc.