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J Nucl Med. 2008; 49 (Supplement 1):82P
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Neurosciences: Basic Science

Imaging Markers of Neuropathology

Preclinical evaluation of [18F]FETA as a new brain hypoxia marker for stroke imaging with PET

Udo Grossmann1, Marianne Patt2, Dietlind Sorger2, Daniel Wagner3, Heike Franke4, Andreas Schildan2, Johannes Boltze3, Frank Emmrich3, Osama Sabri2 and Henryk Barthel2

1 Translational Centre for Regenerative Medicine; 2 Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany; 3 Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany; 4 Rudolph-Boehm-Institute of Pharmacology and Toxicology, University of Leipzig, Leipzig, Germany

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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).





This Article
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Right arrow Articles by Grossmann, U.
Right arrow Articles by Barthel, H.
PubMed
Right arrow Articles by Grossmann, U.
Right arrow Articles by Barthel, H.