TY - JOUR
T1 - Aluminum Fluoride-18 Labeled Mannosylated Dextran
T2 - Radiosynthesis and Initial Preclinical Positron Emission Tomography Studies
AU - Andriana, Putri
AU - Makrypidi, Konstantina
AU - Liljenbäck, Heidi
AU - Rajander, Johan
AU - Saraste, Antti
AU - Pirmettis, Ioannis
AU - Roivainen, Anne
AU - Li, Xiang-Guo
N1 - © 2023. The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - 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 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.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[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 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[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.
AB - 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 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.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[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 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[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.
KW - Male
KW - Rats
KW - Animals
KW - Positron Emission Tomography Computed Tomography
KW - Dextrans
KW - Endothelial Cells
KW - Mannose Receptor
KW - Rats, Sprague-Dawley
KW - Positron-Emission Tomography/methods
KW - Inflammation
KW - Fluorine Radioisotopes/chemistry
KW - PET imaging
U2 - 10.1007/s11307-023-01816-7
DO - 10.1007/s11307-023-01816-7
M3 - Article
C2 - 37016195
SN - 1860-2002
VL - 25
SP - 1094
EP - 1103
JO - Molecular Imaging and Biology
JF - Molecular Imaging and Biology
IS - 6
ER -