TY - JOUR T1 - Using Cerebral White Matter for Estimation of Nondisplaceable Binding of 5-HT<sub>1A</sub> Receptors in Temporal Lobe Epilepsy JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1794 LP - 1800 DO - 10.2967/jnumed.109.063743 VL - 50 IS - 11 AU - Giampiero Giovacchini AU - Shielah Conant AU - Peter Herscovitch AU - William H. Theodore Y1 - 2009/11/01 UR - http://jnm.snmjournals.org/content/50/11/1794.abstract N2 - The estimation of nondisplaceable binding from cerebellar white matter, rather than from whole cerebellum, was proposed for the PET tracer carbonyl-11C-WAY-100635 (N-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}-N-(2-pyridyl)cyclohexanecarboxamidel]) because of the heterogeneity of total ligand binding in this region. For the 5-hydroxytryptamine receptor 1A (5-HT1A) antagonist 18F-N-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}-N-2-pyridyl)trans-4-fluorocyclohexanecarboxamide (18F-FCWAY), the estimation of nondisplaceable binding from cerebellum (VND) may be additionally biased by spillover of 18F-fluoride activity from skull. We aimed to assess the effect of using cerebral white matter as reference region on detection of group differences in 5-HT1A binding with PET and 18F-FCWAY. Methods: In 22 temporal lobe epilepsy patients (TLE) and 10 healthy controls, 18F-FCWAY distribution volume in cerebral white matter (VWM) was computed using an extrapolation method as part of a partial-volume correction (PVC) algorithm. To assess the feasibility of applying this method to clinical studies in which PVC is not performed, VWM was also calculated by placing circular, 6-mm-diameter regions of interest (ROIs) in the centrum semiovalis on parametric images. Binding potentials were BPF = (VT – VND)/fP and BPF-WM = (VT – VWM)/fP, where VT is total distribution volume and fP = 18F-FCWAY plasma free fraction. Statistical analysis was performed using t tests and linear regression. Results: In the whole group, VWM was 14% ± 19% lower than VND (P &lt; 0.05). VWM/fP was significantly (P &lt; 0.05) lower in patients than in controls. All significant (P &lt; 0.05) reductions of 5-HT1A receptor availability in TLE patients detected by BPF were also detected using BPF-WM. Significant (P &lt; 0.05) reductions of 5-HT1A specific binding were detected by BPF-WM, but not BPF, in ipsilateral inferior temporal cortex, contralateral fusiform gyrus, and contralateral amygdala. However, effect sizes were similar for BPF-WM and BPF. The value of VWM calculated with the ROI approach did not significantly (P &gt; 0.05) differ from that calculated with the extrapolation approach (0.67 ± 0.32 mL/mL and 0.72 ± 0.34 mL/mL, respectively). Conclusion: Cerebral white matter can be used for the quantification of nondisplaceable binding of 5-HT1A without loss of statistical power for detection of regional group differences. The ROI approach is a good compromise between computational complexity and sensitivity to spillover of activity, and it appears suitable to studies in which PVC is not performed. For 18F-FCWAY, this approach has the advantage of avoiding spillover of 18F-fluoride activity onto the reference region. ER -