18F-FDR as a New Powerful Radiolabelling Agent for PET

Positron emission tomography (PET) is an important imaging modality used widely in clinical diagnosis and drug development. Fluorine-18 is an ideal isotope for PET applications as it has a relatively long half-life (t1/2 = 109.7 min) and it is readily generated at very high specific activity as [18F]F- fluoride ion in hospital and research centre cyclotrons. One of the current challenges in PET is to efficiently attach a readily available fluorine-18 containing small molecule (prosthetic group) to a peptide, protein or antibody format by bioconjugation through a linker. Clearly, a prosthetic group that can be prepared through easily automated [18F]-FDG-type radiochemistry would offer practical and technical advantages. [18F]-FDG is an attractive candidate for direct peptide conjugation as it is a hydrophilic sugar and it is readily available at PET centres worldwide. However, [18F]-FDG does not conjugate well with peptide linkers under mild conditions. Instead successful reactions require low pH and/or high temperature, and even then extended conjugations times, a combination often incompatible with sensitive small molecules, peptides or biomacromolecules. Recently, it was demonstrated that [18F]-FDR is an efficient ligand for rapid bioconjugations of peptides (Chem. Commun. 2012, in press). A particularly attractive aspect of the method is that unlike [18F]-FDG utilising protocols, there is no requirement for harsh conditions or pre-derivatisation of the [18F]-labelled sugar, and labelling can occur in one step immediately after production of the fluorosugar.  This project will validate this novel exciting technology and exploit its potential in pre-clinical PET Imaging. We will investigate the [18F]-FDR radiolabelling of (1) small molecules, with an emphasis on the imaging of tumour hypoxia; (2) peptides and small proteins with potential use in oncology, CNS or cardiovascular imaging; (3) antibody formats with an emphasis on liver fibrosis.  The resulting [18F]-FDR tracers will be then investigated in vitro and in vivo

Project Team: Prof Matteo Zanda, Prof David O'Hagan

Funding: MSD SULSA PhD Studentship