Analysis of [18F]fluoromannan PET data
Mannan is a general term for structurally variable and complex polysaccharides which are an important part of cell walls of yeasts, fungi, and plants. Common feature of mannans is the high proportion of mannose. Mannose is a C-2 epimer of glucose; it exists in pyranose and furanose forms. Mannose has an important part in glycosylation of human (animal) proteins.
The innate immune system can identify and destroy mannan-containing cells via mannose-binding lectin. Also the mannose receptor (CD206), expressed on the surface of macrophages, dermal fibroblasts, and keratinocytes, identifies terminal mannose in glycoproteins, playing a role in both innate and adaptive immune systems.
Mannan injection causes acute inflammation, and has been used to generate a psoriasis, psoriatic arthritis, and rheumatoid arthritis mouse model (Khmaladze et al, 2014; Hagert et al., 2018). Mannan-conjugated proteins have been studied in immunotherapy and in development of vaccines against cancers and fungal infections.
D-Mannose has been labeled with 18F and studied as a tumour and atherosclerosis imaging tracer (Furumoto et al, 2013; Tahara et al, 2014). Labeled mannose is a substrate similar to [18F]FDG, with uptake dependent on GLUTs and hexokinase, and thus the metabolic activity of the tissue. Mannose receptor has been targeted by mannose-conjugated albumin, dextran, and liposomes labeled with 68Ga and 64Cu; these tracers may be useful in detecting macrophages, and have been used to localize for example lymph nodes (Choi et al, 2011; Locke et al, 2012; Eo et al, 2015; Kang et al, 2015; Lee et al., 2017). [99mTc]tilmanocept is a mannocylated dextran with FDA approval for lymphatic mapping. Li et al (2016) developed 18F-labeled mannan, and found high uptake in atherosclerotic lesions in mice, as well as in macrophage-rich organs in healthy rats.
[18F]fluoromannan PET studies have so far been only in mice and rats, reporting only the SUV (Li et al, 2016). 3 h PET scans showed that SUV reaches reasonably steady level 30-60 min after intravenous administration.
When [18F]fluoromannan is administered intraperitoneally in small mass (2 µg) in mice, the tracer is mainly cleared from circulation into the spleen, liver, thymus, and urine. When [18F]fluoromannan is co-administered with 2 or 10 mg mannan, doses which are used to induce the psoriasis, psoriatic arthritis, and rheumatoid arthritis models, the uptake into spleen and liver is reduced, and radioactivity is observed widely distributed, including the joints, bone marrow, and skin (Hagert et al., 2019).
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Updated at: 2019-02-11
Created at: 2016-05-23
Written by: Vesa Oikonen, Jouni Tuisku