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

• Published in: Molecular imaging and biology 2023-12, Vol.25 (6), p.1094-1103
• Main Authors: Andriana, Putri, Makrypidi, Konstantina, Liljenbäck, Heidi, Rajander, Johan, Saraste, Antti, Pirmettis, Ioannis, Roivainen, Anne, Li, Xiang-Guo
• Format: Article
• Language: English
• Subjects: Aluminum; Aluminum fluorides; Animals; Antigen-presenting cells; Bone marrow; Computed tomography; Dextran; Dextrans; Emission analysis; Endothelial Cells; Fluorides; Fluorine isotopes; Fluorine Radioisotopes - chemistry; Hepatocytes; High performance liquid chromatography; Imaging; Inflammation; Liquid chromatography; Liver; Lymph nodes; Macrophages; Male; Mannose; Mannose Receptor; Mannose receptors; Medical imaging; Medicine; Medicine & Public Health; Photon emission; Positron emission; Positron emission tomography; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography - methods; Radioactivity; Radiochemical analysis; Radiology; Rats; Rats, Sprague-Dawley; Receptors; Research Article; Single photon emission computed tomography; Stability; Tomography
• ISSN: 1536-1632; 1860-2002
• DOI: 10.1007/s11307-023-01816-7

Purpose 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 99m Tc 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 18 F for initial positron emission tomography (PET) studies in rats. Procedures 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 in vivo PET/CT imaging, ex vivo gamma counting, and high-performance liquid chromatography analysis. Results Al[ 18 F]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 in vivo 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 in vivo blocking experiments. Conclusions Our results imply that Al[ 18 F]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. Graphical abstract