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The goal of this study was to develop a suitable kinetic analysis method for quantification of 5-HT 2A  receptor parameters with [ 11 C]MDL 100,907. Twelve control studies and four preblocking studies (400 nmol/kg unlabeled MDL 100,907) were performed in isoflurane-anesthetized rhesus monkeys. The plasma input function was determined from arterial blood samples with metabolite measurements by extraction in ethyl acetate. The preblocking studies showed that a two-tissue compartment model was necessary to fit the time activity curves of all brain regions including the cerebellum—in other words, the need for two compartments is not proof of specific binding. Therefore, a three-tissue compartment model was used to analyze the control studies, with three parameters fixed based on the preblocking data. Reliable fits of control data could be obtained only if no more than three parameters were allowed to vary. For routine use of [ 11 C]MDL 100,907, several simplified methods were evaluated. A two-tissue (2T‘) compartment with one fixed parameter was the most reliable compartmental approach; a one-compartment model failed to fit the data adequately. The Logan graphical approach was also tested and produced comparable results to the 2T’ model. However, a simulation study showed that Logan analysis produced a larger bias at higher noise levels. Thus, the 2T' model is the best choice for analysis of [ 11 C]MDL 100,907 studies.

Kinetic Analysis of the 5-HT2A Ligand [11C]MDL 100,907

Kinetic Analysis of the 5-HT_2A Ligand [¹¹C]MDL 100,907