A clinical trial with (+)-[18F]Flubatine: evaluation of metabolism, plasma protein binding and parameters.

Introduction
(+)-[18F]Flubatine ((+)[18F]NCFHEB), the enantiomer of the recently introduced radioligand for quantificati(-)-[18F]Flubatine, was investigated in a clinical trial with patients suffering from Alzheimer’s disease compared to healthy controls. In order to be able to apply full kinetic modelling biological parameters such as plasma protein binding, amount of parent compound over time and distribution between cellular and noncellular blood components, were determined. In addition the kinetics of the tracer distribution between plasma and whole blood was assessed.
Methods
Plasma protein binding was evaluated in vitro by means of ultracentrifugation using a blood sample from each subject prior to injection. The amount of unchanged tracer over time was determined at 11 time points ranging from 3 to 270 min p.i. by radio-HPLC analysis of protein free plasma obtained by centrifugation as described previously. The distribution of radioactivity between cellular and non-cellular blood components was determined at 11 time points p.i. after separation of the blood components by centrifugation.
Results/Discussion
Plasma protein binding of (-)-[18F]Flubatine was found to be 0.140.02 (meansd) without significant difference between AD and HC groups. Metabolic degradation of (+)-[18F]Flubatine was very low: the amount of parent compound was found to be 100 and 972 % at 90 and 270 min p.i., respectively. The activity distribution between plasma and whole blood was found to be 0.820.05 and did not change with time. Kinetics for the distribution of the tracer between plasma and whole blood was determined over a time period of 1.5 h and equilibrium was found to be reached instantaneously.
Conclusions Biological parameters such as plasma protein binding, metabolism and tracer/activity distribution between plasma and whole blood were investigated within a clinical trial using (+)-[1842 subtype of nAChRs. From the biological data obtained within this study we, conclude that (+)-[18F]Flubatine is a very suitable radiotracer for the determination of the 42 nAChRs by kinetic modelling since plasma protein binding is moderate and the equilibrium between whole blood and plasma is reached instantaneously. Furthermore, metabolic degradation of the radiotracer is negligible.