Macrophage mannose receptor CD206 targeting of fluoride-18 labeled mannosylated dextran: A validation study in mice

Purpose Aluminum fluoride-18-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid-conjugated mannosylated dextran derivative (Al[ 18 F]F-NOTA-D10CM) is a new tracer for PET imaging. We report here on in vitro and in vivo validation of the tracer’s ability to target the macrophage mannose receptor CD206. Methods First, the uptake of intravenously (i.v.) administered Al[ 18 F]F-NOTA-D10CM was compared between wild-type (WT) and CD206 −/− knockout (KO) mice. C57BL/6N mice were injected with complete Freund’s adjuvant (CFA) in the left hind leg and the uptake of Al[ 18 F]F-NOTA-D10CM after i.v. or intradermal (i.d.) injection was studied at 5 and 14 days after CFA induction of inflammation. Healthy C57BL/6N mice were studied as controls. Mice underwent PET/CT on consecutive days with [ 18 F]FDG, i.v. Al[ 18 F]F-NOTA-D10CM, and i.d. Al[ 18 F]F-NOTA-D10CM. After the last imaging, Al[ 18 F]F-NOTA-D10CM was i.v. injected for an ex vivo biodistribution study and autoradiography of inflamed tissues. Blood plasma samples were analyzed using high-performance liquid chromatography. To evaluate the specificity of Al[ 18 F]F-NOTA-D10CM binding, an in vitro competitive displacement study was performed on inflamed tissue sections using autoradiography. CD206 expression was assessed by immunohistochemical staining. Results Compared with WT mice, the uptake of Al[ 18 F]F-NOTA-D10CM was significantly lower in several CD206 −/− KO mice tissues, including liver (SUV 8.21 ± 2.51 vs. 1.06 ± 0.16, P