Detection of Secondary Thalamic Degeneration After Cortical Infarction Using cis-4-18F-Fluoro- D-Proline
Karl-Josef Langen 1*,
Dagmar Salber 2,
Kurt Hamacher 3,
Gabriele Stoffels 2,
Guido Reifenberger 4,
Dirk Pauleit 1,
Heinz H. Coenen 5,
and
Karl Zilles 6
1 Institute of Neuroscience and Biophysics–Medicine, Research Centre Jülich, Jülich, Germany; Brain Imaging Centre West, Research Centre Jülich, Jülich, Germany
2 C. & O. Vogt Institute of Brain Research, Heinrich-Heine-University, Düsseldorf, Germany
3 Brain Imaging Centre West, Research Centre Jülich, Jülich, Germany; Institute of Neuroscience and Biophysics–Nuclear Chemistry, Research Centre Jülich, Jülich, Germany
4 Department of Neuropathology, Heinrich-Heine-University, Düsseldorf, Germany
5 C. & O. Vogt Institute of Brain Research, Heinrich-Heine-University, Düsseldorf, Germany; Institute of Neuroscience and Biophysics–Nuclear Chemistry, Research Centre Jülich, Jülich, Germany
6 Institute of Neuroscience and Biophysics–Medicine, Research Centre Jülich, Jülich, Germany; Brain Imaging Centre West, Research Centre Jülich, Jülich, Germany; C. & O. Vogt Institute of Brain Research, Heinrich-Heine-University, Düsseldorf, Germany
* To whom correspondence should be addressed. E-mail: k.j.langen{at}fz-juelich.de.
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Abstract |
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The amino acid cis-4-18F-fluoro-D-proline (D-cis-18F-FPro) exhibits preferential uptake in the brain compared with its L-isomer, but the clinical potential of the tracer is as yet unkown. In this study we explored the cerebral uptake of D-cis-18F-FPro in rats with focal cortical infarctions. Methods: Focal cortical infarctions were induced in different areas of the cortex of 20 Fisher CDF rats by photothrombosis (PT). At variable time points after PT (1 d to 4 wk), the rats were injected intravenously with D-cis-18F-FPro. For comparison, 12 rats were injected simultaneously with 3H-deoxyglucose (3H-DG), 3 rats were injected with 3H-methyl-L-methionine (3H-MET), and 2 rats were injected with 3H-PK11195. Within 2 h after injection of the tracers, coronal cryosections of the brains were produced and evaluated by dual-tracer autoradiography. Lesion-to-brain ratios (L/B ratios) were calculated by dividing the maximal uptake in areas with increased tracer uptake by the mean uptake in normal brain tissue. Histologic slices were stained by toluidine blue and by immunostainings for glial fibrillary acidic protein (GFAP), CD68 for macrophages, and CD11b for microglia. Results: Prominent uptake of D-cis-18F-FPro was found in ipsilateral thalamic nuclei (TN) and partially in the corpus striatum starting at 3 d after infarction with increasing L/B ratios up to 4 wk (mean L/B ratio ± SD, 6.7 ± 3.5). The involved TN varied with the site of the cortical lesion corresponding to their thalamocortical projections connecting them with their specific target region in the cerebral cortex. The TN were positive for CD11b and GFAP from day 7 onward, whereas uptake of 3H-DG, 3H-MET, and 3H-PK11195 and immunostaining for CD68 were similar to that of normal brain. Furthermore, increased uptake of D-cis-18F-FPro was found in the area of the cortical infarctions (mean L/B ratio ± SD, 12.1 ± 8.1). From day 5 onward, the pattern of uptake was congruent with that of immunostaining for CD11b and CD68 but was different from that of GFAP. Conclusion: D-cis-18F-FPro appears to be a sensitive PET tracer for detection of secondary degeneration of TN after cortical injury. The uptake mechanisms of D-cis-18F-FPro remain to be elucidated, but the relationship to microglial activation suggests a diagnostic potential in various brain diseases.
Key Words:
cis-4-18F-fluoro-D-proline, cortical infarction, thalamic degeneration, PET, microglia
