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Change in Binding Potential as a Quantitative Index of Neurotransmitter Release Is Highly Sensitive to Relative Timing and Kinetics of the Tracer and the Endogenous Ligand

¹ Division of Research, Section of Imaging Science, Department of Radiology, Indiana University School of Medicine, Indianapolis, Indiana
² Department of Biomedical Engineering, Purdue School of Engineering and Technology, Indiana University—Purdue University, Indianapolis, Indiana

View larger version (14K): [in a new window]   FIGURE 1. (A) Idealized DA perturbations with identical DA peak times used in simulated 11C-raclopride scans. BP (B) and bound endogenous DA (C), corresponding to different DA release for each perturbation shown in A. Dashed line at 44 nmol/L indicates Bmax(tot).

View larger version (14K): [in a new window]   FIGURE 2. (A) Idealized DA perturbations as approximate -functions used in 11C-raclopride simulations. (B) BP resulting from each approximate -function, plotted vs. time of onset (td). (C) Free tissue raclopride, FRAC(t), curve over time for a case of no DA perturbation (baseline).

View larger version (24K): [in a new window]   FIGURE 3. Timing of cocaine-induced (A) and mp-induced (B and C) endogenous DA responses used as perturbations in 11C-raclopride simulations. Bold lines indicate reference responses (DA responses beginning at t = 0 of the simulated scan). Note that the x-axes start at –20 min (i.e., 20 min before start of simulations).

View larger version (17K): [in a new window]   FIGURE 4. (A) BP for cocaine-induced and mp-induced DA responses with respect to timing of each perturbation. (B) Identical data set shown in A, normalized by BP from a reference perturbation (Fig. 3) initiated at t = 0 for each DA curve type.

View larger version (20K): [in a new window]   FIGURE 5. (A) -Variate functions representing CDP I at multiple times. Height of peak corresponds to 42.0 nmol/L bound endogenous DA, with corresponding transient maximum receptor occupancy of 95%. (B) -Variate functions representing CDP II at multiple times. Height of peak corresponds to 39.8 nmol/L bound endogenous DA, with corresponding transient maximum receptor occupancy of 90%. (C) BP for CDP I () and CDP II () as responses are delayed in time relative to bolus 11C-raclopride injection.

View larger version (17K): [in a new window]   FIGURE 6. Correlation between BP and EWA for multiple DA responses CDP I (sharp response; , ) and CDP II (blunt response; , •) with 2 different versions of raclopride kinetics. Tracer A parameters are from Pappata et al. (35) (, •) and tracer B parameters were modified from Endres and Carson (21) (, ). The 2 squares (, ) represent data points from simulations generated with a -variate DA perturbation with the following parameters: = 1.5; ß = 0.2; = 10,000; td = 1. This corresponds to a huge and physiologically implausible release of DA.

View larger version (17K): [in a new window]   FIGURE 7. Simulation results from hypothetical experiment comparing plausible DA perturbations. (A) CDP I (sharp curve, solid line) and CDP II (blunt curve, dashed line) were used as DA perturbations. CDP I (sharp), DA takeoff t = 2 min; CDP II (blunt), DA takeoff t = 1 min after simulated bolus 11C-raclopride injection. (B) Corresponding DA release (left y-axis) and BP (right y-axis) for curves in A. CDP I, ; CDP II, .