PMID- 19837769
OWN - NLM
STAT- MEDLINE
DCOM- 20091203
LR  - 20211020
IS  - 1535-5667 (Electronic)
IS  - 0161-5505 (Print)
IS  - 0161-5505 (Linking)
VI  - 50
IP  - 11
DP  - 2009 Nov
TI  - Using cerebral white matter for estimation of nondisplaceable binding of 5-HT1A 
      receptors in temporal lobe epilepsy.
PG  - 1794-800
LID - 10.2967/jnumed.109.063743 [doi]
AB  - The estimation of nondisplaceable binding from cerebellar white matter, rather 
      than from whole cerebellum, was proposed for the PET tracer 
      carbonyl-(11)C-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-HT(1A)) antagonist 
      (18)F-N-2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl-N-2-pyridyl)trans-4-fluorocyclohexanecarboxamide 
      ((18)F-FCWAY), the estimation of nondisplaceable binding from cerebellum (V(ND)) 
      may be additionally biased by spillover of (18)F-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-HT(1A) binding with PET and (18)F-FCWAY. 
      METHODS: In 22 temporal lobe epilepsy patients (TLE) and 10 healthy controls, 
      (18)F-FCWAY distribution volume in cerebral white matter (V(WM)) 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, V(WM) was also calculated by placing circular, 
      6-mm-diameter regions of interest (ROIs) in the centrum semiovalis on parametric 
      images. Binding potentials were BP(F) = (V(T) - V(ND))/f(P) and BP(F-WM) = (V(T) 
      - V(WM))/f(P), where V(T) is total distribution volume and f(P) = (18)F-FCWAY 
      plasma free fraction. Statistical analysis was performed using t tests and linear 
      regression. RESULTS: In the whole group, V(WM) was 14% +/- 19% lower than V(ND) 
      (P < 0.05). V(WM)/f(P) was significantly (P < 0.05) lower in patients than in 
      controls. All significant (P < 0.05) reductions of 5-HT(1A) receptor availability 
      in TLE patients detected by BP(F) were also detected using BP(F-WM). Significant 
      (P < 0.05) reductions of 5-HT(1A) specific binding were detected by BP(F-WM), but 
      not BP(F), in ipsilateral inferior temporal cortex, contralateral fusiform gyrus, 
      and contralateral amygdala. However, effect sizes were similar for BP(F-WM) and 
      BP(F). The value of V(WM) calculated with the ROI approach did not significantly 
      (P > 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-HT(1A) 
      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 (18)F-FCWAY, this approach has the advantage of 
      avoiding spillover of (18)F-fluoride activity onto the reference region.
FAU - Giovacchini, Giampiero
AU  - Giovacchini G
AD  - Department of Nuclear Medicine, S. Andrea Hospital, La Spezia, Italy. 
      giampiero.giovacchini@asl5.liguria.it
FAU - Conant, Shielah
AU  - Conant S
FAU - Herscovitch, Peter
AU  - Herscovitch P
FAU - Theodore, William H
AU  - Theodore WH
LA  - eng
GR  - Z01 NS002236-33/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
DEP - 20091016
PL  - United States
TA  - J Nucl Med
JT  - Journal of nuclear medicine : official publication, Society of Nuclear Medicine
JID - 0217410
RN  - 0 (Carbon Radioisotopes)
RN  - 0 (Piperazines)
RN  - 0 (Pyridines)
RN  - 112692-38-3 (Receptor, Serotonin, 5-HT1A)
RN  - 71IH826FEG 
      (N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide)
SB  - IM
MH  - Adult
MH  - Brain/anatomy & histology/*metabolism
MH  - Carbon Radioisotopes
MH  - Case-Control Studies
MH  - Cerebellum/metabolism
MH  - Epilepsy, Temporal Lobe/diagnosis/*metabolism
MH  - Female
MH  - Humans
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Piperazines/chemistry/metabolism
MH  - Protein Binding
MH  - Pyridines/chemistry/metabolism
MH  - Receptor, Serotonin, 5-HT1A/*metabolism
MH  - Time Factors
PMC - PMC3059591
MID - NIHMS278381
EDAT- 2009/10/20 06:00
MHDA- 2009/12/16 06:00
PMCR- 2011/03/17
CRDT- 2009/10/20 06:00
PHST- 2009/10/20 06:00 [entrez]
PHST- 2009/10/20 06:00 [pubmed]
PHST- 2009/12/16 06:00 [medline]
PHST- 2011/03/17 00:00 [pmc-release]
AID - jnumed.109.063743 [pii]
AID - 10.2967/jnumed.109.063743 [doi]
PST - ppublish
SO  - J Nucl Med. 2009 Nov;50(11):1794-800. doi: 10.2967/jnumed.109.063743. Epub 2009 
      Oct 16.