Measurement of PET Tracers Low Activity Levels During Plasma Samples Analysis

Plasma metabolite analysis in the PET (Positron Emission Tomography) studies requires quantification of very low levels of radioactive materials during a rapid and sequential passage of plasma samples. Quantification is necessary for deriving a kinetic model that describes the transport and metabolism of the administered radiotracer in the body. Using kinetic models, information about a particular biological process in the human body can be determined from the concentration of the PET tracer in the blood plasma and tissues, during the PET scan. To estimate the kinetic model parameters, the amount of the parent compound in plasma at a given time point is needed. The plasma contains the original drug (parent compound) and its metabolite that was produced by enzymatic activity; therefore, metabolism of the radio-labeled tracer results in radioactive metabolites that cannot be differentiated from the parent compound, because both, the metabolite and the parent compound, carry the same radioactive isotope and emit photons with the same energy (511 keV). The total plasma radioactivity and the radiotracer decay time are known, but in order to define the kinetic model, an adjustment for the actual un metabolized (parent) radiotracer requires correction at each time point. Metabolite analysis of the radiotracer includes blood sample collection with a known time stamp, separation of the plasma by centrifugation, separation of the plasma into its compounds (parent and metabolite) by High Pressure Liquid Chromatography (HPLC), and analysis by a radiation detector (radio- HPLC) to determine the percentage of the unchanged drug (parent compound). The detector system records the activity levels in the HPLC output line for each compound during the plasma analysis procedure (the metabolites as well as the original un metabolized radiotracer). Our goal was to design a high sensitivity measuring system to improve the detection level of the positron-emitting isotope and enhance metabolite analysis