TY - JOUR T1 - Ex Vivo Tracing of NMDA and GABA-A Receptors in Rat Brain After Traumatic Brain Injury Using <sup>18</sup>F-GE-179 and <sup>18</sup>F-GE-194 Autoradiography JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1442 LP - 1447 DO - 10.2967/jnumed.115.167403 VL - 57 IS - 9 AU - Francisco López-Picón AU - Anniina Snellman AU - Olena Shatillo AU - Paula Lehtiniemi AU - Tove J. Grönroos AU - Päivi Marjamäki AU - William Trigg AU - Paul A. Jones AU - Olof Solin AU - Asla Pitkänen AU - Merja Haaparanta-Solin Y1 - 2016/09/01 UR - http://jnm.snmjournals.org/content/57/9/1442.abstract N2 - In vivo imaging of N-methyl-d-aspartate (NMDA) glutamate receptor and γ-aminobutyric acid (GABA)-A receptor during progression of brain pathology is challenging because of the lack of imaging tracers with high affinity and specificity. Methods: We monitored changes in NMDA receptor and GABA-A receptor in a clinically relevant model of traumatic brain injury (TBI) induced by lateral fluid percussion in adult rats, using 2 new ligands for PET: 18F-GE-179 for the open/active state of the NMDA receptor ion channel and 18F-GE-194 for GABA-A receptor. Ex vivo brain autoradiography of radioligands was performed at subacute (5–6 d) and chronic (40–42 d) time points after TBI. Results: At 5–6 d after TBI, 18F-GE-179 binding was higher in the cortical lesion area, in the lesion core, and in the hippocampus than in the corresponding contralateral regions; this increase was probably related to increased permeability of the blood–brain barrier. At 40–42 d after TBI, 18F-GE-179 binding was significantly higher in the medial cortex, in the corpus callosum, and in the thalamus than in the corresponding contralateral regions. Five to 6 days after TBI, 18F-GE-194 binding was significantly higher in the lesion core and significantly lower in the ipsilateral thalamus. By 40–42 d after TBI, the reduction in 18F-GE-194 binding extended to the cortical lesion, including the perilesional cortex around the lesion core. The reduction in thalamic binding was more extensive at 40–42 d than at 5–6 d after TBI, suggesting a progressive decrease in thalamic GABA-A receptor density. Immunohistochemistry against GABA-A α1 subunit revealed a similar decrease to 18F-GE-194 binding, particularly during the chronic phase. Conclusion: Our data support the validity of novel 18F-GE-179 and 18F-GE-194 radioligands for the detection of changes in active NMDA receptor and GABA-A receptor in the injured brain. These tools are useful for follow-up evaluation of secondary postinjury pathologies. ER -