Master of Science - Research
Department of Chemistry
Sarowi, Suzilawati Muhd, 18F radiolabelling of carbohydrates using click chemistry for the development of new anticancer imaging agents for positron emission tomography, Master of Science - Research thesis, Department of Chemistry, University of Wollongong, 2010. http://ro.uow.edu.au/theses/3621
The objective of this study was to utilise click chemistry to develop novel types of 18F labelled carbohydrates for use in positron emission tomography imaging through the coupling of [18F]-fluoroalkynes with various 1-azido sugars and 2-azido sugars. In total, eight novel compounds were synthesized in this study.
The products of the click reaction between various types of alkynes and 1-azido sugars, the 1,2,3-triazole sugars, were afforded in good yields. Two hydroxy triazole sugars prepared in this manner were fluorinated and used as cold standards for HPLC analysis and identification of the analogous radiolabelled material. It was subsequently demonstrated that 1-azido glucosamine could be succesfully labelled with fluorine-18 in just 8 mins via a click reaction using 4-[18F]-fluoro-1-butyne.
The above work was then extended to the preparation of 2-azido sugar triazoles, which widens the scope of click reactions on 2-azido sugars as only a few examples have been reported in the literature. Further extension of the work to the conjugation of 1-azido glucosamine and 1-azido glucuronide methyl ester with an acetylenic phenol, provided new examples of sugar triazole compounds which might be labelled with fluorine-18 using the same methods as those used to radiolabel the well known imaging agent fluoroethyltyrosine.
In summary, the click reaction is a very useful method for radiolabelling carbohydrates, which can be achieved in short reaction times and in good yield. The methodology that was developed here can be used to modify various bioactive peptides with radiolabelled carbohydrates to generate new types of cancer imaging agents.