PET-labelled phosphonium cations for mitochondria imaging

Abstract

This thesis details the characterisation of lipophilic cation radiotracers for biomedical imaging. The radiotracers discussed are based on triphenylphosphonium cations which can accumulate in the mitochondria and are radiolabelled with either [18F] or [11C]. Implementation of existing radiotracers and development of novel [11C] based di- phosphonium di-cation radiotracers is described in Chapter 3. The chemistry required to produce precursors, reference compounds and radiolabelling is discussed and resulted in implementation of three existing [18F] radiotracers and development of four novel [11C] radiotracers. The later chapters focus on assessment of biological properties of the tracers. This is achieved through studies carried out in vitro, including characterisation in cells and work carried out on an isolated perfused heart model, as well as in vivo studies. In all biological systems radiotracers were assessed under standard conditions and under challenge conditions. The challenge conditions included treatment with a mitochondrial membrane uncoupler, mitochondrial complex inhibitor and a chemotherapy agent. Alteration in radiotracer properties were compared between radiotracers. This work provides a strong foundation for justifying the translation of one of the investigated compounds into man.