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

• Type of Material: Article
• Authors: Malgorzata Lipowska, Emory University; Nashwa Jarkas, Emory University; Ronald Voll, Emory University; Jonathon Nye, Emory University; Jeffrey Klenc, Emory University; Mark Goodman, Emory University; Andrew Taylor Jr., Emory University
• Language: English
• Date: 2018-03-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 Elsevier Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.nucmedbio.2017.12.001
• Title of Journal or Parent Work: Nuclear Medicine and Biology
• ISSN: 0969-8051
• Volume: 58
• Start Page: 42
• End Page: 50
• Grant/Funding Information: This research was supported by the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases grant R37 DK038842.
• Keywords: Science & Technology; STRUCTURAL-CHARACTERIZATION; COMPLEXES; LIGANDS; RADIOPHARMACEUTICALS; IMAGING AGENTS; Renal radiotracer; VOLUNTEERS; Biodistribution; Re(CO)(3)([F-18]FEDA); POSITRON-EMISSION-TOMOGRAPHY; I-131 OIH; Life Sciences & Biomedicine; IN-VIVO EVALUATION; Radiolabeling; Radiology, Nuclear Medicine & Medical Imaging; INITIAL EVALUATION; PET imaging
• Research Categories: Health Sciences, Radiology

Abstract

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.