Aluminum Fluoride-18 Labeled Mannosylated Dextran: Radiosynthesis and Initial Preclinical Positron Emission Tomography Studies

Abstract

<p><strong>Purpose: </strong>In addition to being expressed on liver sinusoidal endothelial cells, mannose receptors are also found on antigen-presenting cells, including macrophages, which are mainly involved in the inflammation process. Dextran derivatives of various sizes containing cysteine and mannose moieties have previously been labeled with ^99mTc and used for single-photon emission computed tomography imaging of sentinel lymph nodes. In this study, we radiolabeled 21.3-kDa D10CM with positron-emitting ¹⁸F for initial positron emission tomography (PET) studies in rats.</p><p><strong>Procedures: </strong>D10CM was conjugated with 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) chelator and radiolabeled with the aluminum fluoride-18 method. The whole-body distribution kinetics and stability of the intravenously administered tracer were studied in healthy male Sprague-Dawley rats by <em>in vivo</em> PET/CT imaging, <em>ex vivo</em> gamma counting, and high-performance liquid chromatography analysis.</p><p><strong>Results: </strong>Al[¹⁸F]F-NOTA-D10CM was obtained with a radiochemical purity of >99% and molar activity of 9.9 GBq/μmol. At 60 minutes after injection, an average of 84% of the intact tracer was found in the blood, indicating excellent <em>in vivo</em> stability. The highest radioactivity concentration was seen in the liver, spleen, and bone marrow, in which mannose receptors are highly expressed under physiological conditions. The uptake specificity was confirmed with <em>in vivo</em> blocking experiments.</p><p><strong>Conclusions: </strong>Our results imply that Al[¹⁸F]F-NOTA-D10CM is a suitable tracer for PET imaging. Further studies in disease models with mannose receptor CD206-positive macrophages are warranted to clarify the tracer's potential for imaging of inflammation.<br></p><p><strong>Keywords: </strong>Dextran; Fluorine-18; Mannose; Mannose receptor; PET.<br></p>