Kinetic analysis of the 5-HT2A ligand [C-11]MDL 100,907

The goal of this study was to develop a suitable kinetic analysis method fo r quantification of 5-HT2A receptor parameters with [C-11]MDL 100,907. Twel ve control studies and foul preblocking studies (400 nmol/kg unlabeled MDL 100,907) were performed in isoflurane-anesthetized rhesus monkeys. The plas ma input function was determined from arterial blood samples with metabolit e measurements by extraction in ethyl acetate. The preblocking studies show ed that a two-tissue compartment model was necessary to fit the time activi ty curves of all brain regions including the cerebellum-in other words, the need fur two compartments is not proof of specific binding. Therefore, a t hree-tissue compartment model was used to analyze the control studies, with three parameters fixed based on the preblocking data. Reliable fits of con trol data could be obtained only if no more than three parameters were allo wed to vary. For routine use of [C-11]MDL 100,907, several simplified metho ds were evaluated. A two-tissue (2T') compartment with one fixed parameter was the most reliable compartmental approach: a one-compartment model faile d to fit the data adequately. The Logan graphical approach was also tested and produced comparable results to the 2T' model. However, a simulation stu dy showed that Logan analysis produced a larger bias at higher noise levels . Thus, the 2T' model is the best choice for analysis of [C-11]MDL 100,907 studies.