UNLABELLED: 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'). CONCLUSION: 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.
UNLABELLED: 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'). CONCLUSION: 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: Masahiro Fujita; Andrea Varrone; Kyeong Min Kim; Hiroshi Watabe; Sami S Zoghbi; Nicholas Seneca; Dnyanesh Tipre; John P Seibyl; Robert B Innis; Hidehiro Iida Journal: Eur J Nucl Med Mol Imaging Date: 2004-01-17 Impact factor: 9.236
Authors: Robert M Kessler; Neil D Woodward; Patrizia Riccardi; Rui Li; M Sib Ansari; Sharlett Anderson; Benoit Dawant; David Zald; Herbert Y Meltzer Journal: Biol Psychiatry Date: 2009-02-28 Impact factor: 13.382