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.
Change in binding potential (deltaBP) is often used to indicate alterations in neurotransmitter concentration in response to stimuli. Increasingly, it is being used in bolus studies as a quantitative index of dopamine (DA) release. In bolus studies, however, BP is an average quantity over time that is influenced by the dynamics of both the tracer and the neurotransmitter. We sought to characterize the sensitivity of deltaBP to changes in endogenous DA concentration and to elucidate possible biases in deltaBP with respect to timing of task-induced or drug-induced increases in DA.


METHODS
Noiseless simulations of (11)C-raclopride PET curves were performed in a specific binding region with concomitant increases in endogenous DA. DA changes were modeled as delta-functions, gamma-variates, or as realistic drug-induced increases in DA over time, based on published results. Graphical estimation of BP with a reference region as the input function was used, with a multilinear formulation of the operational equation.


RESULTS
Simulations demonstrated that deltaBP (a). is linear over a narrow range of integrated DA release, (b). has an inherent sensitivity to timing of DA perturbations, and (c). could incorrectly infer the relative amounts of DA released between subject populations or experimental conditions. These results are explained by what we term the effective weighted availability, which describes the interaction of a DA function and free raclopride concentration over time and follows directly from earlier work.


CONCLUSIONS
We illustrate how, under quite plausible circumstances, deltaBP may lead to erroneous conclusions about relative amounts of DA released after dopaminergic perturbations. Our findings caution against using deltaBP as a quantitative or rank index of DA release when comparing different dopaminergic stimuli.
Yoder
Karmen K
KK
Department of Radiology, Indiana University School of Medicine, Indianapolis, Indiana, USA. kkyoder@iupui.edu
Wang
Chunzhi
C
Morris
Evan D
ED
D001665:Binding Sites; D001921:Brain / Q000000981:diagnostic imaging*; D002250:Carbon Radioisotopes; D003198:Computer Simulation; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D018377:Neurotransmitter Agents / Q000378:metabolism*; D020891:Raclopride; D011869:Radioligand Assay; D013997:Time Factors; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D018377:Neurotransmitter Agents; D020891:Raclopride; D004298:Dopamine