Project 1.2 Neuroreceptor ligand targeting for PET imaging
Epilepsy is a common brain disorder that is estimated to affect 1-2% of Australians. The disorder involves repeated brain seizures caused by nerve cells producing electrical signals at up to four times the normal rate. Causes include head injuries, brain tumours, prenatal brain damage and some genetic and infectious illnesses, but about half of all cases have no apparent cause.
Epilepsy attacks are associated with disturbances in the functioning of a class of neuroreceptors known as central benzodiazepine receptors. By attaching a radiolabel to flumazenil, a benzodiazepine antagonist that binds to these receptors, researchers can use PET to investigate epilepsy and other neurodegenerative diseases. Studying the onset of epilepsy in animal models will aid the development of treatments that interfere with the epileptic processes rather than simply suppressing seizures.
ANSTO and the Peter MacCallum Cancer Institute previously established a useful method for synthesising Fluorine-18 flumazenil. The groups are now working with other CRC BID participants to evaluate the chemical and biological stability of four flumazenil derivatives and determine their pharmacokinetic and biodistribution profiles. Following assessment of the value of the flumazenil derivatives as PET imaging agents in animal models, the most promising candidate will then undergo clinical trials.
