Graphical analysis and simplified quantification of striatal and extrastriatal dopamine D2 receptor binding with [123I]epidepride SPECT

Masanori Ichise, Masahiro Fujita, John P. Seibyl, N. Paul, L. G. Verhoeff, Ronald M. Baldwin, Sami S. Zoghbi, Nallakkandi Rajeevan, Dennis S. Charney, Robert B. Innis

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34 Scopus citations

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 (R(T)) 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' = (α(RR)/(P) - α(RF)/(P), V3' = (1 + δ) (α(RR) - α(RF)) and R(T) = V3'/(V2/(P)' + δV2/(M)'), where α is a regression coefficient, δ is the equilibrium area ratio of M and P, and (V2(P')N2(M')) are the corresponding nondisplaceable distribution volumes. V3' by simplified analysis (SA) was calculated from R(T) determined without blood data and (V2/(P)' + δV2/(M)') 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≥ 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≤ 0.65) because of significant intersubject variability (23%) in (V2/(P)' + δV2/(U)'). 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 R(T) suffers as a measure of D2 binding from significant intersubject variability in the metabolite- contributed distribution volume of the nondisplaceable compartment.

Original languageEnglish (US)
Pages (from-to)1902-1912
Number of pages11
JournalJournal of Nuclear Medicine
Volume40
Issue number11
StatePublished - Nov 1999

Keywords

  • Dopamine D receptors
  • Graphical analysis
  • Metabolite correction
  • SPECT quantification
  • [I]epidepride

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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