Investigation of polymer-modified microelectrodes as sensors for the determination of radiopharmaceutical analogs

Radiopharmaceuticals are used in nuclear medicine to image specific organs for the purpose of diagnosis. Many radiopharmaceuticals consist of {dollar}sp{lcub}rm 99m{rcub}{dollar}Tc coordinated with ligands that impart chemical characteristics which cause the complex to target a specific organ when injected into a patient. A sensor placed into the organ may help to elucidate the in vivo mechanism(s) of action for existing and potential {dollar}sp{lcub}rm 99m{rcub}{dollar}Tc radiopharmaceuticals. The in vivo sensor employed must be small and also specific for the analyte of interest. The use of a very small electrode, or microelectrode, in which the diameter of the conductive material is less than 25 {dollar}mu{dollar}m allows for determination of electroactive species with very little perturbation to the media under investigation. Furthermore, coating the microelectrode with a polymer film can impart chemical selectivity for the analyte of interest based on the properties of the polymer selected.; Methods for the fabrication and polymer modification of carbon fiber disk shaped microelectrodes are described here. Microelectrode fabrications based on the use of fluorinated polymers is presented. Initial constructions rely on heat sealing the electroactive material in dual shrink/melt poly(tetrafluoroethylene) (PTFE) tubing under vacuum. This provides for a microelectrode with an overall diameter of 1.5 mm. The use of both plasma polymerization of PTFE and Teflon AF-S allow for the construction of microelectrodes with an overall diameter of less than 10 {dollar}mu{dollar}m. These methods should provide for a sensor to be implanted into a test animal with minimal damage to the surrounding tissue.; The advantages of using PTFE tubing over previously reported methods include (1) a rigid yet flexible shield, (2) elimination of fillers (i.e. epoxy), and (3) chemical inertness. Another advantage is that the PTFE shield may be activated to provide a support upon which polymers of interest may be grafted. The microelectrodes constructed were placed in methanolic solutions of styrene and gamma irradiated at 5 Mrads to graft polymerize the monomer to the surface. The poly(styrene) was subsequently sulfonated with chlorosulfonic acid to form poly(styrene sulfonate). Poly(styrene sulfonate) modified microelectrodes were evaluated with the test analyte Ru(NH{dollar}sb3)sb6{dollar}Cl{dollar}sb3{dollar} and also with (Re(DMPE){dollar}sb3{dollar}) CF{dollar}sb3{dollar}SO{dollar}sb3{dollar}. This compound is a nonradioactive analog of (Tc(DMPE){dollar}sb3{dollar}) CF{dollar}sb3{dollar}SO{dollar}sb3{dollar} which has shown uptake in the heart tissue of test animals.; The electrochemical behavior of (Re(DIARS){dollar}sb2{dollar}Cl{dollar}sb2{dollar}) Cl, a nonradioactive analog of (Tc(DIARS){dollar}sb2{dollar}Cl{dollar}sb2{dollar}) Cl which has shown uptake in the brain is the focus of the last chapter. The electrochemistry of this complex at gold electrodes was performed and compared with spectroelectrochemistry obtained at a gold minigrid. The development of Nafion coated electrodes as possible sensors for this compound is discussed. Results for optimization, calibration curves, and interference studies are presented.