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Introduction: Our previous work demonstrated that the 99m Tc renal tracer, 99m Tc(CO) 3 (FEDA) ( 99m Tc-1), has a rapid clearance comparable in rats to that of 131 I-OIH, the radioactive gold standard for the measurement of effective renal plasma flow. The uncharged fluoroethyl pendant group of 99m Tc-1 provides a route to the synthesis of a structurally analogous rhenium-tricarbonyl 18 F renal imaging agent, Re(CO) 3 ([ 18 F]FEDA) ( 18 F-1). Our goal was to develop an efficient one-step method for the preparation of 18 F-1 and to compare its pharmacokinetic properties with those of 131 I-OIH in rats., Methods: 18 F-1 was prepared by the nucleophilic 18 F-fluorination of its tosyl precursor. The labeled compound was isolated by HPLC and subsequently evaluated in Sprague-Dawley rats using 131 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: 18 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 131 I-OIH, with minimal hepatic/gastrointestinal elimination. The activity in the urine, as a percentage of 131 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 18 F-1 through the kidneys and into the bladder; there was no demonstrable activity in bone verifying the absence of free [ 18 F]fluoride., Conclusions: 18 F-1 exhibited a high specificity for the kidney, rapid renal excretion comparable to that of 131 I-OIH and high in vivo radiochemical stability. Not only is 18 F-1 a promising PET renal tracer, but it provides a route to the development of a pair of analogous 18 F/ 99m Tc renal imaging agents with almost identical structures and comparable pharmacokinetic properties. These promising in vivo results warrant subsequent evaluation in humans., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: 99m Tc(CO) 3 -nitrilotriacetic acid, 99m Tc(CO) 3 (NTA), is a new renal tubular agent with pharmacokinetic properties comparable to those of 131 I-OIH but the clearance of 99m Tc(CO) 3 (NTA) and 131 I-OIH is still less than the clearance of PAH, the gold standard for the measurement of effective renal plasma flow. At physiological pH, dianionic 99m Tc(CO) 3 (NTA) has a mononegative inner metal-coordination sphere and a mononegative uncoordinated carboxyl group. To evaluate alternate synthetic approaches, we assessed the importance of an uncoordinated carboxyl group, long considered essential for tubular transport, by evaluating the pharmacokinetics of three analogs with the 99m Tc(CO) 3 (NTA) metal-coordination sphere but with uncharged pendant groups., Methods: 99m Tc(CO) 3 complexes with N-(2-acetamido)iminodiacetic acid (ADA), N-(2-hydroxyethyl)iminodiacetic acid (HDA) and N-(fluoroethyl)iminodiacetic acid (FEDA) were prepared using a tricarbonyl kit and isolated by HPLC. The pharmacokinetics were evaluated in Sprague-Dawley rats, with 131 I-OIH as an internal control; urine was analyzed for metabolites. Plasma protein binding and erythrocyte uptake were determined from the 10min blood samples. Re(CO) 3 (FEDA), the analog of 99m Tc(CO) 3 (FEDA), was prepared and characterized., Results: 99m Tc(CO) 3 (ADA), 99m Tc(CO) 3 (HDA) and 99m Tc(CO) 3 (FEDA) were efficiently prepared as a single species with high radiochemical purities (>99%). These new monoanionic 99m Tc(CO) 3 tracers with uncharged dangling groups all showed rapid blood clearance and high specificity for renal excretion. Activity in the urine, as a percent of 131 I-OIH at 10 and 60min, was 96% and 99% for ADA, 96% and 100% for HDA, and 100% and 99% for FEDA, respectively. Each new tracer was excreted unchanged in the urine. The Re(CO) 3 (FEDA) structure adds compelling evidence that such 99m Tc(CO) 3 (NTA) analogs have metal-coordination spheres identical to that of 99m Tc(CO) 3 (NTA)., Conclusions: New tracers lacking the negatively charged pendant carboxyl group previously thought to be essential for rapid renal extraction, 99m Tc(CO) 3 (ADA), 99m Tc(CO) 3 (HDA) and 99m Tc(CO) 3 (FEDA), exhibit pharmacokinetics in rats comparable to those of 99m Tc(CO) 3 (NTA) and 131 I-OIH. Furthermore, these encouraging results in rats warrant evaluation of this new tracer type in humans., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: Renal scintigraphy is an important imaging modality for the diagnosis and management of a variety of renal diseases including obstruction and renovascular hypertension as well as the evaluation of absolute and relative kidney function. The goal of this work was to evaluate Al(18)F-NODA-butyric acid (Al(18)F-1) as a potential PET tracer to image the kidneys and monitor renal function by comparing its pharmacokinetic properties with those of (131)I-o-iodohippurate ((131)I-OIH), the radioactive standard for the measurement of effective renal plasma flow., Methods: Al(18)F-1 was prepared in aqueous conditions using a one-pot Al(18)F-radiofluorination method and its radiochemical purity was determined by HPLC. Biodistribution studies, using (131)I-OIH as an internal control, were performed in normal rats and in rats with renal pedicle ligation. In vitro stability and metabolism of Al(18)F-1 were analyzed by HPLC. Dynamic microPET/CT studies were conducted in normal rats., Results: Al(18)F-1 showed excellent stability in vitro and in vivo. Biodistribution studies in normal rats and in rats with simulated renal failure confirmed that Al(18)F-1 was exclusively cleared through the renal-urinary pathway and that the hepatic/gastrointestinal activity was less for Al(18)F-1 than for (131)I-OIH both at 10 and 60 min. Dynamic PET showed a rapid transit of Al(18)F-1 through the kidneys into the bladder., Conclusion: These results suggest that the easily labeled Al(18)F-based compounds provide a highly promising approach for the development of a PET renal radiotracer that combines superior imaging qualities with a reliable measure of effective renal plasma flow., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Introduction: The first human studies of a characterized radiopharmaceutical containing a {(99m)Tc(CO)(3)}(+) core, Na[(99m)Tc(CO)(3)(LAN)], demonstrated that Na[(99m)Tc(CO)(3)(LAN)] was an excellent renal imaging agent; however, its clearance was less than that of (131)I-orthoiodohippurate ((131)I-OIH), and it did not provide a direct measure of effective renal plasma flow. In order to develop a (99m)Tc renal agent with pharmacokinetic properties equivalent to those of (131)I-OIH, we investigated the (99m)Tc(CO)(3)/Re(CO)(3) complexes formed from carboxymethylmercaptosuccinic acid (CMSAH(3)) and thiodisuccinic acid (TDSAH(4)). Once the ligand is bound to (99m)Tc(CO)(3) through a thioether and two carboxyl groups, the complexes have at least one unbound carboxyl group, essential for the interaction with the renal tubular transporter., Methods: X-ray crystal structural analysis of [NMe(4)][Re(CO)(3)(CMSAH)] was performed to interpret the nature of (99m)Tc tracers. CMSAH(3) and TDSAH(4) were radiolabeled by incubating each ligand and the precursor [(99m)Tc(CO)(3)(H(2)O)(3)](+) at 70 degrees C (pH 7) for 30 min. The products were purified by reversed-phase high-performance liquid chromatography, and biodistribution studies were performed in Sprague-Dawley rats, with (131)I-OIH as an internal control at 10 and 60 min., Results: Radiolabeling CMSAH(3) and TDSAH(4) with the [(99m)Tc(CO)(3)(H(2)O)(3)](+) precursor gave products quantitatively. Analysis of the Re(CO)(3) complexes with the CMSAH(3) and TDSAH(4) ligands demonstrates that ligands are bound in (99m)Tc/Re(CO)(3) complexes through a thioether and two deprotonated carboxyl groups (forming tridentate dianionic moieties, generally with two 5-membered chelate rings). Renal excretion at 60 min (activity in the urine as a percentage of (131)I-OIH) was 68+/-1% for Na(3)[(99m)Tc(CO)(3)(TDSA)] but was 98+/-1% for Na(2)[(99m)Tc(CO)(3)(CMSA)]., Conclusion: In rats, Na(2)[(99m)Tc(CO)(3)(CMSA)] is extracted by the kidneys and eliminated in the urine almost as rapidly as (131)I-OIH; consequently, Na(2)[(99m)Tc(CO)(3)(CMSA)] may provide a direct measure of effective renal plasma flow, and further evaluation in humans is warranted.