title: The assessment of the non-equilibrium effect in the 'Patlak analysis' of Fdopa PET studies.
abstract: 'Patlak analysis' is a common approach used in Fdopa PET studies to calculate the uptake constant (Ki) of the tracer. It is assumed in the Patlak analysis that the reversible compartment of tissue radioactivity used is in effective equilibrium with the tracer in plasma. Therefore, using the data prior to equilibrium is in conflict with the assumption, and its effect on the estimate thus needs to be examined. In this study, we used simulations to investigate the errors due to the violation of the equilibrium assumption. Two factors affecting the estimate of Ki were examined--the eigenvalue of the model response function and the shape of the input function. The Ki estimate obtained from the Patlak analysis was found to be markedly biased because the system is not in equilibrium during the first 2 h post Fdopa injection. The magnitude of the bias was found to be dependent on the time interval used in the analysis (10% difference when comparing results from intervals 30-120 min and 60-120 min) and on the eigenvalue of the response function (10% change in Ki when the eigenvalue was changed by 20% around the nominal value). The estimates are also affected by the intersubject variations in the plasma time-activity curves. Therefore, Patlak analysis users should interpret their results with caution, particularly when examining small intersubject differences and small changes due to physiological or pharmacological interventions.
authors.affiliation: Department of Molecular and Medical Pharmacology, University of California, Los Angeles, USA.
authors.forename: D C
authors.initials: DC
authors.lastname: Yu
authors.forename: S C
authors.initials: SC
authors.lastname: Huang
authors.forename: J R
authors.initials: JR
authors.lastname: Barrio
authors.forename: M E
authors.initials: ME
authors.lastname: Phelps
mesh_terms: D001812:Blood-Brain Barrier; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D003198:Computer Simulation; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D005462:Fluorine Radioisotopes / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D008961:Models, Structural; D011859:Radiography; D012016:Reference Values; D014055:Tomography, Emission-Computed / Q000379:methods*
chemical_list: D005462:Fluorine Radioisotopes; C029112:5-fluorodopa; D004295:Dihydroxyphenylalanine