Chemoenzymatic radiosynthesis of 2-deoxy-2-[ 18 F]fluoro-d-trehalose ([ 18 F]-2-FDTre): A PET radioprobe for in vivo tracing of trehalose metabolism.

Autor: Peña-Zalbidea S; Dept. Bioingeniería e Ingeniería Aeroespacial, Universidad Carlos III de Madrid, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain., Huang AY; Department of Chemistry and Biochemistry, Central Michigan University, Mount Pleasant, MI, United States., Kavunja HW; Department of Chemistry and Biochemistry, Central Michigan University, Mount Pleasant, MI, United States., Salinas B; Dept. Bioingeniería e Ingeniería Aeroespacial, Universidad Carlos III de Madrid, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain., Desco M; Dept. Bioingeniería e Ingeniería Aeroespacial, Universidad Carlos III de Madrid, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain., Drake C; SOFIE Co, Culver City, CA, United States., Woodruff PJ; Department of Chemistry, University of Southern Maine, Portland, ME, United States., Vaquero JJ; Dept. Bioingeniería e Ingeniería Aeroespacial, Universidad Carlos III de Madrid, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain. Electronic address: jjvaquer@ing.uc3m.es., Swarts BM; Department of Chemistry and Biochemistry, Central Michigan University, Mount Pleasant, MI, United States. Electronic address: ben.swarts@cmich.edu.
Jazyk: angličtina
Zdroj: Carbohydrate research [Carbohydr Res] 2019 Jan 15; Vol. 472, pp. 16-22. Date of Electronic Publication: 2018 Nov 04.
DOI: 10.1016/j.carres.2018.11.002
Abstrakt: Trehalose analogues bearing fluorescent and click chemistry tags have been developed as probes of bacterial trehalose metabolism, but these tools have limitations with respect to in vivo imaging applications. Here, we report the radiosynthesis of the 18 F-modified trehalose analogue 2-deoxy-2-[ 18 F]fluoro-d-trehalose ([ 18 F]-2-FDTre), which in principle can be used in conjunction with positron emission tomography (PET) imaging to allow in vivo imaging of trehalose metabolism in various contexts. A chemoenzymatic method employing the thermophilic TreT enzyme from Thermoproteus tenax was used to rapidly (15-20 min), efficiently (70% radiochemical yield; ≥ 95% radiochemical purity), and reproducibly convert the commercially available radiotracer 2-deoxy-2-[ 18 F]fluoro-d-glucose ([ 18 F]-2-FDG) into the target radioprobe [ 18 F]-2-FDTre in a single step; both manual and automated syntheses were performed with similar results. Cellular uptake experiments showed that radiosynthetic [ 18 F]-2-FDTre was metabolized by Mycobacterium smegmatis but not by various mammalian cell lines, pointing to the potential future use of this radioprobe for selective PET imaging of infections caused by trehalose-metabolizing bacterial pathogens such as M. tuberculosis.
(Copyright © 2018. Published by Elsevier Ltd.)
Databáze: MEDLINE
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