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Published on: January 11, 2020
(18)F-Labeling of Mannan for Inflammation Research with Positron Emission Tomography
Xiang-Guo Li1, Cecilia Hagert2, Riikka Siitonen3
1Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, FI-20520 Turku, Finland; Turku PET Centre, Åbo Akademi University, Kiinamyllynkatu 4-8, FI-20520 Turku, Finland.
Abstract:
Recently mannan from Saccharomyces cerevisiae has been shown to be able to induce psoriasis and psoriatic arthritis in mice, and the phenotypes resemble the corresponding human diseases. To investigate the pathological processes, we set out to label mannan with fluorine-18 ((18)F) and study the (18)F-labeled mannan in vitro and in vivo with positron emission tomography (PET). Accordingly, mannan has been transformed into (18)F-fluoromannan with (18)F-bicyclo[6.1.0]nonyne. In mouse aorta, the binding of [(18)F]fluoromannan to the atherosclerotic lesions was clearly visualized and was significantly higher compared to blocking assays (P < 0.001) or healthy mouse aorta (P < 0.001). In healthy rats the [(18)F]fluoromannan radioactivity accumulated largely in the macrophage-rich organs such as liver, spleen, and bone marrow and the excess excreted in urine. Furthermore, the corresponding (19)F-labeled mannan has been used to induce psoriasis and psoriatic arthritis in mice, which indicates that the biological function of mannan is preserved after the chemical modifications.
Insights
Mannan from Saccharomyces cerevisiae induces psoriasis and psoriatic arthritis. Researchers developed fluorine-18 labeled mannan for imaging, visualizing its binding to atherosclerotic lesions in mice.
Area of Science:
- Immunology
- Radiochemistry
- Medical Imaging
Background:
- Mannan from Saccharomyces cerevisiae is implicated in inducing psoriasis and psoriatic arthritis in mouse models.
- These induced phenotypes closely mimic human inflammatory diseases, suggesting mannan's role in pathogenesis.
Purpose of the Study:
- To develop a fluorine-18 ((18)F) labeled mannan for in vitro and in vivo imaging using positron emission tomography (PET).
- To investigate the distribution and binding characteristics of (18)F-fluoromannan in biological systems.
Main Methods:
- Synthesis of (18)F-fluoromannan via click chemistry using (18)F-bicyclo[6.1.0]nonyne.
- In vivo imaging of (18)F-fluoromannan in mouse aorta with atherosclerotic lesions.
- Assessment of (18)F-fluoromannan distribution in healthy rats, focusing on macrophage-rich organs.
- Confirmation of biological activity using (19)F-labeled mannan to induce disease models.
Main Results:
- [(18)F]fluoromannan successfully visualized atherosclerotic lesions in mouse aorta with significantly higher binding compared to controls (P < 0.001).
- In healthy rats, radioactivity accumulated in macrophage-rich organs (liver, spleen, bone marrow) and was excreted via urine.
- The (19)F-labeled mannan retained its ability to induce psoriasis and psoriatic arthritis, confirming preserved biological function.
Conclusions:
- Fluorine-18 labeled mannan is a viable radiotracer for imaging atherosclerotic lesions using PET.
- (18)F-fluoromannan distribution highlights its uptake in macrophage-rich tissues, relevant for inflammatory disease research.
- Chemical modification for radiolabeling preserves mannan's pathogenic role in psoriasis and psoriatic arthritis models.
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