New Lipophilic Cations for Imaging Apoptosis and the Mitochondria

The project aims to develop a new range of PET tracers to allow imaging of the mitochondria. It is suitable for a chemist interested in synthetic inorganic and organic chemistry, who also wants to gain radiochemistry and biology skills. New chemistry and radiochemistry methodology will feature (i) the design of functionalised chelates to stabilise Ga-68 centres and facilitate an overall cationic charge following complexation and (ii) 18F-fluorination of lipophilic phosphonium cations. Biological evaluation of the tracers will involve the Langendorff perfused, isolated heart model to allow analysis of tracer pharmacokinetics and blood-flow.

The project falls squarely within the remit of the CDT, namely by developing novel tools to investigate and image an important biomedical phenomenon (i.e. mitochondrial failure associated with apoptosis, disease or drug toxicity), as well as providing comprehensive chemistry, biology and radiochemistry training.

Apoptosis is the most common form of programmed cell death and is a key mechanism in many pathological diseases. These include
cancer, diabetes, neurodegenerative disorders and aging. Being able to fully understand this mechanism could lead to huge advances in detection, drug development and treatment. Currently there are very few non-invasive techniques capable of quantifying and assessing the process of apoptosis in humans. The discovery that mitochondria play an important role in the early stages of apoptosis has directed focus to targeting the mitochondria as a means of identifying disease. Changes in mitochondrial membrane potential can be directly related to mitochondrial dysfunction, representing a biophysical process that could be targeted with imaging.