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

The purpose of this study was to assess the reproducibility of repeated pos itron emission tomography (PET) measures of brain monoamine oxidase B (MAO B) using deuterium-substituted [C-11]L-deprenyl ([C-11]L-deprenyl-D2) in no rmal subjects and to validate the method used for estimating the kinetic co nstants from the irreversible 3-compartment model applied to the tracer bin ding, Five normal healthy subjects (age range 23-73 years) each received tw o PET scans with [C-11]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 lambda k(3), a model term prop ortional to MAO B, and K-1, the plasma to brain transfer constant that is r elated to blood flow. Linear (LIN) and nonlinear least-squares (NLLSR) esti mation methods were used to calculate the optimum model constants, A compar ison 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 lambda k( 3) showed a difference between scan 1 and scan 2 in the global value rangin g between -6.97 and 4.5% (average -2.1 +/- 4.7%). The average percent chang e for eight brain regions for the five subjects was -2.84 +/- 7.07%. Values of lambda k(3) for scan 1 and scan 2 were highly correlated (r(2) = 0.98; p < 0.0001; slope 0.955). Similarly, values of K-1 showed a significant cor relation between scan 1 and scan 2 (r(2) = 0.61; e < 0.0001; slope 0.638) t hough the values for scan 2 were generally lower than those of scan 1, Ther e was essentially no difference between the values of model constants calcu lated using the NLLSQ or LIN methods, Regional brain uptake of [C-11]L-depr enyl-D2 varied between scan 1 and scan 2, driven by the differences in arte rial tracer input. Application of a 3-compartment model to regional time-ac tivity data and arterial input function yielded lambda k(3) values for scan 1 and scan 2 with an average difference of -2.84 +/- 7.07%. Linear regress ion applied to values of hk, from the LIN and NLLSR methods validated the u se of the linear method for calculating hk,. NUCL MED BIOL 21;1:43-49, 2000 . (C) 2000 Elsevier Science Inc. All rights reserved.