Reproducibility of repeated measures of deuterium substituted [11C]L-deprenyl ([11C]L-deprenyl-D2) binding in the human brain

Jean Logan, Joanna S. Fowler, Nora D. Volkow, Gene Jack Wang, Robert R. MacGregor, Colleen Shea

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37 Scopus citations

Abstract

The purpose of this study was to assess the reproducibility of repeated positron emission tomography (PET) measures of brain monoamine oxidase B (MAO B) using deuterium-substituted [11C]L-deprenyl ([11C]L-deprenyl-D2) in normal subjects and to validate the method used for estimating the kinetic constants from the irreversible 3-compartment model applied to the tracer binding. Five normal healthy subjects (age range 23-73 years) each received two PET scans with [11C]L-deprenyl-D2. The time interval between scans was 7-27 days. Time-activity data from eight regions of interest and an arterial plasma input function was used to calculate λk3, a model term proportional to MAO B, and K1, the plasma to brain transfer constant that is related to blood flow. Linear (LIN) and nonlinear least-squares (NLLSQ) estimation methods were used to calculate the optimum model constants. A comparison of time-activity curves for scan 1 and scan 2 showed that the percent of change for peak uptake varied from -18.5 to 15.0% and that increases and decreases in uptake on scan 2 were associated with increases and decreases in the value of the arterial input of the tracer. Calculation of λk3 showed a difference between scan 1 and scan 2 in the global value ranging between -6.97 and 4.5% (average -2.1 ± 4.7%). The average percent change for eight brain regions for the five subjects was -2.84 ± 7.07%. Values of λk3 for scan 1 and scan 2 were highly correlated (r2 = 0.98; p < 0.0001; slope 0.955). Similarly, values of K1 showed a significant correlation between scan 1 and scan 2 (r2 = 0.61; p < 0.0001; slope 0.638) though the values for scan 2 were generally lower than those of scan 1. There was essentially no difference between the values of model constants calculated using the NLLSQ or LIN methods. Regional brain uptake of [11C]L-deprenyl-D2 varied between scan 1 and scan 2, driven by the differences in arterial tracer input. Application of a 3-compartment model to regional time-activity data and arterial input function yielded λk3 values for scan 1 and scan 2 with an average difference of -2.84 ± 7.07%. Linear regression applied to values of λk3 from the LIN and NLLSQ methods validated the use of the linear method for calculating λk3. Copyright (C) 2000 Elsevier Science Inc.

Original languageEnglish
Pages (from-to)43-49
Number of pages7
JournalNuclear Medicine and Biology
Volume27
Issue number1
DOIs
StatePublished - Jan 2000
Externally publishedYes

Keywords

  • Kinetic model
  • Monoamine oxidase
  • PET
  • [11C]L-deprenyl-D2

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