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Radiosynthesis of new PET tracer targeting macrophage mannose receptor

List of AuthorsAndriana Putri, Palani Senthil, Fair-Mäkelä Ruth, Makrypidi Konstantina, Liljenbäck Heidi, Kärnä Salli, Salmi Marko, Pirmettis Ioannis, Saraste Antti, Li Xiang-Guo, Roivainen Anne

Conference nameInternational Symposium on Radiopharmaceutical Science 2022

PlaceCité des Congrès Nantes

Publication year2022

Journal acronymNuc Med and Biol

Title of seriesApplications of radiolabeled compounds in other fields

Volume number108-109

Start pageS62

End pageS63

Number of pages2



Objective: Mannose receptor CD206 is expressed on alternatively activated macrophages1 . The aim of this study, was to develop a new 18F-labelled mannosylated dextran derivative, [18F]AlF-NOTA-DCM, for PET imaging of macrophage mannose receptor (MMR), and to evaluate its feasibility to detect inflammation.

Methods: DCM consisting a dextran backbone, cysteine and mannose moieties was synthesized as previously described2. For initial cell binding studies, a fluorophore Alexa488 tetrafluorophenyl ester was conjugated to DCM precursor in phosphate-buffered saline by 15 minutes incubation at room temperature (1 mg/mL). Then, human blood monocytes were in vitro polarized into M1 and M2 macrophages, and binding of Alexa488-DCM was evaluated by flow cytometry. For PET studies, DCM was first conjugated with 1,4,7 triazacyclononane-1,4,7 triacetic acid (NOTA) chelator. 18F was first attached to Aluminum to form Al18F, and then incubated with NOTA-DCM at 100°C for 13 minutes. In vivo stability of intravenously injected [18F]AlF-NOTA-DCM was assessed in healthy C57BL/6NRJ mice and high-performance liquid chromatography (HPLC) analysis of plasma samples. Feasibility of [18F]AlF-NOTA-DCM to detect inflammation was evaluated in a Complete Freund’s Adjuvant induced mouse model of lymph node and foot pad inflammation.

Results: The flow cytometry showed that M2 macrophages expressing MMR clearly took up Alexa488-DCM, whereas M1 macrophages lacking MMR did not show uptake (Fig. 1b). [18F]AlF-NOTADCM (25 kDa, Fig. 1a) was synthesized with >99% radiochemical purity and stability shelf life of 4 hours. Tracer was highly stable in mouse blood circulation (at 10 min post-injection 90%±6 of plasma radioactivity was from intact tracer). In vitro blocking study with excess of unlabeled DCM on inflamed lymph node tissue section confirmed that [18F]AlF-NOTA-DCM binding was specific to CD206+ macrophages. With 18F-FDG as reference, PET/CT revealed that [18F] AlF-NOTA-DCM visualized the inflamed foci (TBR 9.60±4.02) with a rapid blood clearance and the highest radioactivity concentration in liver, spleen and bone marrow, respectively. H&E and CD206 staining confirmed the uptake in inflamed area.

Conclusion: A new macrophage mannose receptor-targeted radiotracer [18F]AlF-NOTA-DCM was successfully developed and showed promising results in preclinical studies to detect inflammation. Further studies in inflammation models are warranted

Last updated on 2023-23-11 at 11:24