RT Journal Article
SR Electronic
T1 Detection of Secondary Thalamic Degeneration After Cortical Infarction Using <em>cis</em>-4-<sup>18</sup>F-Fluoro- <span class="sc">d</span>-Proline
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1482
OP 1491
DO 10.2967/jnumed.107.041699
VO 48
IS 9
A1 Karl-Josef Langen
A1 Dagmar Salber
A1 Kurt Hamacher
A1 Gabriele Stoffels
A1 Guido Reifenberger
A1 Dirk Pauleit
A1 Heinz H. Coenen
A1 Karl Zilles
YR 2007
UL http://jnm.snmjournals.org/content/48/9/1482.abstract
AB 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.