Re(CO)^sub 3^([^sup 18^F]FEDA), a novel ^sup 18^F PET renal tracer: Radiosynthesis and preclinical evaluation

Introduction: Our previous work demonstrated that the 99mTc renal tracer, 99mTc(CO)3(FEDA) (99mTc-1), has a rapid clearance comparable in rats to that of 131I-OIH, the radioactive gold standard for the measurement of effective renal plasma flow. The uncharged fluoroethyl pendant group of 99mTc-1 pro...

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Published inNuclear medicine and biology Vol. 58; p. 42
Main Authors Lipowska, Malgorzata, Jarkas, Nashwa, Voll, Ronald J, Nye, Jonathon A, Klenc, Jeffrey, Goodman, Mark M, Taylor, Andrew T
Format Journal Article
LanguageEnglish
Published Oxford Elsevier BV 01.03.2018
Subjects
Bladder
Computed tomography
Erythrocytes
Evaluation
Excretion
Fluorides
Fluorination
Fluorine isotopes
Gold standard
High-performance liquid chromatography
In vivo methods and tests
Kidneys
Liquid chromatography
Medical imaging
Metabolites
Organs
Pharmacology
Positron emission
Positrons
Radioactive tracers
Radiochemical analysis
Rats
Renal function
Rhenium
Stability
Tomography
Urine
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Summary:Introduction: Our previous work demonstrated that the 99mTc renal tracer, 99mTc(CO)3(FEDA) (99mTc-1), has a rapid clearance comparable in rats to that of 131I-OIH, the radioactive gold standard for the measurement of effective renal plasma flow. The uncharged fluoroethyl pendant group of 99mTc-1 provides a route to the synthesis of a structurally analogous rhenium-tricarbonyl 18F renal imaging agent, Re(CO)3([18F]FEDA) (18F-1). Our goal was to develop an efficient one-step method for the preparation of 18F-1 and to compare its pharmacokinetic properties with those of 131I-OIH in rats. Methods: 18F-1 was prepared by the nucleophilic 18F-fluorination of its tosyl precursor. The labeled compound was isolated by HPLC and subsequently evaluated in Sprague-Dawley rats using 131I-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: 18F-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 131I-OIH, with minimal hepatic/gastrointestinal elimination. The activity in the urine, as a percentage of 131I-OIH, was 92% and 95% at 10 and 60min, respectively. All other organs (heart, spleen, lungs) showed a negligible tracer uptake (<0.4% ID). Dynamic microPET/CT imaging demonstrated rapid transit of 18F-1 through the kidneys and into the bladder; there was no demonstrable activity in bone verifying the absence of free [18F]fluoride. Conclusions: 18F-1 exhibited a high specificity for the kidney, rapid renal excretion comparable to that of 131I-OIH and high in vivo radiochemical stability. Not only is 18F-1 a promising PET renal tracer, but it provides a route to the development of a pair of analogous 18F/99mTc renal imaging agents with almost identical structures and comparable pharmacokinetic properties. These promising in vivo results warrant subsequent evaluation in humans.
ISSN:0969-8051
1872-9614