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

Research output: Contribution to journalArticle

33 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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