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Studies towards metabolically stable Fluorine-18 labelled peptides and their efficient syntheses

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posted on 28.03.2022, 16:11 by Brendan J. Evans
Positron emission tomography (PET) is a powerful nuclear medicine imaging technique that has become invaluable for the in vivo diagnosis and staging of cancers and many other diseases. The overall aim of this project was to develop strategies for improving the metabolic stability and ease of synthesis of 18F radiolabelled peptide conjugates for use in PET. The first objective was to use model systems to determine if the substitution of an amide bond with a sulfonamide bond increases the metabolic stability of peptide conjugates. For this, N-benzoyl glycine and N-benzenesulfonyl glycine were incubated with the human carboxylesterase/amidase model enzyme pig liver esterase. Both compounds exhibited good stability, however, future work with other enzyme systems would be valuable. The second objective was to synthesise a series of bifunctional aromatic and heteroaromatic compounds that possess the good leaving group tetramethylammonium (TMA) and an activated 4-nitrophenyl ester to enable efficient fluorination and peptide conjugation. Unfortunately, the 4-nitrophenyl ester proved to be too active, making it difficult to form the TMA activated aromatic systems. As a result, a new method was developed based upon the synthesis of TMA methyl esters. Using this method, the synthesis of a TMA bearing methyl ester was successfully trialled.


Table of Contents

1. Introduction -- 2. Comparative stability of amide and sulfonamide model systems -- 3. Studies towards efficient direct labelling of peptides with Fluorine-18 -- 4. Materials and methods -- 5. Conclusions and future directions -- Appendices.


Theoretical thesis. "A thesis submitted in partial fulfillment of the requirements for the degree of Master of Research"--title page. Bibliography: pages 46-51

Awarding Institution

Macquarie University

Degree Type

Thesis MRes


MRes, Macquarie University, Faculty of Science and Engineering, Department of Chemistry and Molecular Sciences

Department, Centre or School

Department of Chemistry and Molecular Sciences

Year of Award


Principal Supervisor

Joanne Jamie


Copyright Brendan John Evans 2018. Copyright disclaimer: http://mq.edu.au/library/copyright




1 online resource (vi, 53 pages : illustrations)

Former Identifiers

mq:70786 http://hdl.handle.net/1959.14/1267721