title: Graphical analysis and simplified quantification of striatal and extrastriatal dopamine D2 receptor binding with [123I]epidepride SPECT.
abstract: The purpose of this study was to extend the graphical analysis of reversible tracer binding to account for labeled lipophilic metabolites (metabolites) in quantifying [123I]epidepride binding to striatal and extrastriatal D2 receptors and, additionally, to evaluate the feasibility of simplified analysis to measure the specific volume of distribution (V3') using single-sample blood data because the tissue ratio (RT) may be a less reliable measure of D2 binding in the presence of metabolites.
  
  
  METHODS
  Multilinear regression analysis (MLRA) and graphical analysis (GA) using plasma parent (P) plus metabolite (M) activities as input and time activities of receptor-free (RF, cerebellum) and receptor-containing regions (RR, striatum and temporal cortex) derived V3' = (alpha(RR)(P) - alpha(RF)(P)), V3' = (1 + delta) (alpha(RR) - alpha(RF)) and RT = V3'/(V2P' + deltaV2M'), where alpha is a regression coefficient, delta is the equilibrium area ratio of M and P, and (V2P'/V2M') are the corresponding nondisplaceable distribution volumes. V3' by simplified analysis (SA) was calculated from RT determined without blood data and (V2P' + deltaV2M') with single-blood sample data. The accuracy of these three V3' values was assessed relative to the metabolite-accounted kinetic analysis (KA) for [123I]epidepride SPECT studies of 11 healthy volunteers, in which each participant had 27 scans and 30 plasma samples drawn during the 14 h after injection.
  
  
  RESULTS
  All three V3' values (mL/g) significantly correlated with those by KA (r > or = 0.90) (striatum/temporal cortex: MLRA, 77.8 +/- 36.6/2.35 +/- 1.16; GA, 98.8 +/- 34.2/4.61 +/- 1.77; SA, 83.9 +/- 24.8/4.26 +/- 1.74; KA, 107.6 +/- 34.4/5.61 +/- 1.84). However, the correlation between RT and V3' was only moderate (r < or = 0.65) because of significant intersubject variability (23%) in (V2P' + deltaV2M').
  
  
  CONCLUSIONS
  The graphical analysis can be extended to account for metabolites in measuring D2 binding with [123I]epidepride SPECT for both high and low D2 density regions. Additionally, simplified V3' measurements with single blood sampling are feasible and may be a practical alternative to the tissue ratio RT because RT suffers as a measure of D2 binding from significant intersubject variability in the metabolite-contributed distribution volume of the nondisplaceable compartment.
authors.affiliation: Department of Nuclear Medicine, Mount Sinai Hospital, and University of Toronto, Ontario, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Ichise
authors.forename: M
authors.initials: M
authors.lastname: Fujita
authors.forename: J P
authors.initials: JP
authors.lastname: Seibyl
authors.forename: N P
authors.initials: NP
authors.lastname: Verhoeff
authors.forename: R M
authors.initials: RM
authors.lastname: Baldwin
authors.forename: S S
authors.initials: SS
authors.lastname: Zoghbi
authors.forename: N
authors.initials: N
authors.lastname: Rajeevan
authors.forename: D S
authors.initials: DS
authors.lastname: Charney
authors.forename: R B
authors.initials: RB
authors.lastname: Innis
mesh_terms: D000328:Adult; D001549:Benzamides; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D003287:Contrast Media; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007457:Iodine Radioisotopes; D008297:Male; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2 / Q000032:analysis* / Q000378:metabolism; D012044:Regression Analysis; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D001549:Benzamides; D003287:Contrast Media; D007457:Iodine Radioisotopes; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; C063525:epidepride