Effect of Dopamine Loss and the Metabolite 3-O-Methyl-[18F]Fluoro-dopa on the Relation between the 18F-Fluorodopa Tissue Input Uptake Rate Constant Kocc and the [18F]Fluorodopa Plasma Input Uptake Rate Constant Ki

Abstract

Parkinson disease is characterized by the loss of dopaminergic neurons, thus decreasing the system's ability to produce and store dopamine (DA). Such ability is often investigated using 18F-fluorodopa (FD) positron emission tomography. A commonly used model to investigate the DA synthesis and storage rate is the modified Patlak graphical approach. This approach allows for both plasma and tissue input functions, yielding the respective uptake rate constants Ki and Kocc. This method requires the presence of an irreversible compartment and the absence of any nontrapped tracer metabolite. In the case of Kocc, this last assumption is violated by the presence of the FD metabolite 3- O-methyl-[18F]fluoro-dopa (3OMFD), which makes the Kocc evaluation susceptible to a downward bias. It was found that both Ki and Kocc are influenced by DA loss and thus are not pure measures of DA synthesis and storage. In the case of Kocc, the presence of 3OMFD exacerbates the effect of DA egress, thus introducing a disease-dependent bias in the Kocc determination. These findings imply that Ki and Kocc provide different assessments of disease severity and that, as disease progresses, Ki and especially Kocc become more related to DA storage capacity and less to the DA synthesis rate.