Project 1.4 Apoptotic pathway targeting for PET imaging
Apoptosis is a process that regulates the number of cells in normal tissues and removes damaged or surplus cells. Failure of normal apoptosis is an important mechanism of some cancers. In other cases, increased apoptosis of functional cells may cause disease.
Ligands that target the apoptotic pathway are a useful alternative to metabolic tracers such as FDG. They can provide valuable information to assist the personalised management of cancer and the development of neuroprotective drugs for stroke and other neurodegenerative diseases.
The best apoptotic imaging agents currently available are based on Fluorine-18 and Idonine-124 ligands that generally yield relatively low signals and do not readily penetrate the blood-brain barrier.
CRC BID participants (ANSTO, Peter MacCallum Cancer Centre, Monash University and Cyclotek) are developing alternative apoptotic imaging agents based on peptide and non-peptide skeletons. These are small molecules with good blood-brain barrier penetration, giving access to neurodegenerative pathologies.
The work involves preparing and characterising tracers that target the apoptotic pathway, and evaluating their clinical and biological stability, pharmacokinetics and biodistribution profiles. In conjunction with new PET detector technology developed by CRC BID participants (see Project 2.1), the tracers will be assessed for their effectiveness and specificity as PET imaging agents for a number of disorders in animal models. The most promising candidates will then undergo further development and validation for clinical evaluation and commercialisation.
