Re(CO)([F]FEDA), a novel F PET renal tracer: Radiosynthesis and preclinical evaluation.

Introduction: Our previous work demonstrated that the Tc renal tracer, Tc(CO)(FEDA) (Tc-1), has a rapid clearance comparable in rats to that of I-OIH, the radioactive gold standard for the measurement of effective renal plasma flow. The uncharged fluoroethyl pendant group of Tc-1 provides a route to the synthesis of a structurally analogous rhenium-tricarbonyl F renal imaging agent, Re(CO)([F]FEDA) (F-1). Our goal was to develop an efficient one-step method for the preparation of F-1 and to compare its pharmacokinetic properties with those of I-OIH in rats.

Methods: F-1 was prepared by the nucleophilic F-fluorination of its tosyl precursor. The labeled compound was isolated by HPLC and subsequently evaluated in Sprague-Dawley rats using I-OIH as an internal control and by dynamic PET/CT imaging. Plasma protein binding (PPB) and erythrocyte uptake (RCB) were determined and the urine was analyzed for metabolites.

Results: F-1 was efficiently prepared as a single species with high radiochemical purity (>99%) and it displayed high radiochemical stability in vitro and in vivo. PPB was 87% and RCB was 21%. Biodistribution studies confirmed rapid renal extraction and high specificity for renal excretion, comparable to that of I-OIH, with minimal hepatic/gastrointestinal elimination. The activity in the urine, as a percentage of I-OIH, was 92% and 95% at 10 and 60 min, respectively. All other organs (heart, spleen, lungs) showed a negligible tracer uptake (<0.4% ID). Dynamic microPET/CT imaging demonstrated rapid transit of F-1 through the kidneys and into the bladder; there was no demonstrable activity in bone verifying the absence of free [F]fluoride.

Conclusions: F-1 exhibited a high specificity for the kidney, rapid renal excretion comparable to that of I-OIH and high in vivo radiochemical stability. Not only is F-1 a promising PET renal tracer, but it provides a route to the development of a pair of analogous F/Tc renal imaging agents with almost identical structures and comparable pharmacokinetic properties. These promising in vivo results warrant subsequent evaluation in humans.