Graphical analysis and simplified quantification of striatal and extrastriatal dopamine D-2 receptor binding with [I-123]epidepride SPECT

The purpose of this study was to extend the graphical analysis of reversibl e tracer binding to account for labeled lipophilic metabolites (metabolites ) in quantifying [I-123]epidepride binding to striatal and extrastriatal D- 2 receptors and, additionally, to evaluate the feasibility of simplified an alysis to measure the specific volume of distribution (V-3') using single-s ample blood data because the tissue ratio (RT) may be a less reliable measu re of D-2 binding in the presence of metabolites. Methods: Multilinear regr ession analysis (MLRA) and graphical analysis (GA) using plasma parent (P) plus metabolite (M) activities as input and time activities of receptor-fre e (RF, cerebellum) and receptor-containing regions (RR, striatum and tempor al cortex) derived V-3' = (alpha(RR)(P) - alpha(RF)(P)), V-3' = (1 + delta) (alpha(RR) - alpha(RF)) and R-T = V-3'/ (V-2(P)' + delta V-2(M)'), where a lpha is a regression coefficient, delta is the equilibrium area ratio of M and P, and (V-2(P)'/V) are the corresponding nondisplaceable distribution v olumes. V-3' by simplified analysis (SA) was calculated from R-T determined without blood data and (V-2(P)' + delta V-2(M)') with single-blood sample data. The accuracy of these three V-3' values was assessed relative to the metabolite-accounted kinetic analysis (KA) for [I-123]epidepride SPECT stud ies 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 V -3' values (mL/g) significantly correlated with those by KA (r greater than or equal to 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 R-T and V- 3' was only moderate (r less than or equal to 0.65) because of significant intersubject variability (23%) in (V-2(P)' + delta V-2(M)'). Conclusion: Th e graphical analysis can be extended to account for metabolites in measurin g D-2 binding with [I-123]epidepride SPECT for both high and low D-2 densit y regions. Additionally, simplified V-3' measurements with single blood sam pling are feasible and may be a practical alternative to the tissue ratio R -T because R-T suffers as a measure of D-2 binding from significant intersu bject variability in the metabolite-contributed distribution volume of the nondisplaceable compartment.