Positron emission tomography: imaging and quantification of neurotransporter availability

Over the last decade, a large number of radiotracers have been developed to image and quantify transporter availability with positron emission tomography (PET) or single-photon emission computed tomography (SPECT). Radiotracers suitable to image dopamine transporters (DATs) and serotonin transporters (SERTs) have been the object of most efforts. Following a brief overview of DAT and SERT radiotracers that have been demonstrated to be suitable for quantitative analysis in vivo, this article describes the principal methods that have been used for the analysis of these data. Kinetic modeling is the most direct implementation of the compartment models, but with some tracers accurate input function measurement and good compartment configuration identification can be difficult to obtain. Other methods were designed to overcome some particular vulnerability to error of classic kinetic modeling, but introduced new vulnerabilities in the process. Reference region methods obviate the need for arterial plasma measurement, but are not as robust to violations of the underlying modeling assumptions as methods using the arterial input function. Graphical methods give estimates of distribution volumes without the requirement of compartment model specification, but provide a biased estimator in the presence of statistical noise. True equilibrium methods are quite robust, but their use is limited to experiments with tracers that are suitable for constant infusion. In conclusion, no universally "best" method is applicable to all neurotransporter imaging studies, and careful evaluation of model-based methods is required for each radiotracer.