We have previously completed a project funded through the Prostate Cancer Foundation of Australia, in which we developed and tested a novel tracer for positron emission tomography (PET) scanning. This tracer is the female sex hormone estradiol (E2) to which a positron-emitting isotope, 18F, has been attached. The 18F-E2 tracer has been tested and we have made the remarkable discovery that it binds only to the ERalpha and not ERbeta subtype of the estrogen receptor (ER). The significance of this is described below. Certain cancers express one or both of the ER subtypes and differences in signalling through these receptors can lead to profound changes in cancer biology: for example, in prostate cancer ERalpha signalling worsens the malignant behaviour of the cells and ERbeta signalling has beneficial effects. Cancers can also express mutant or other variant forms of the estrogen receptor. We have previously transfected the ERalpha and ERbeta genes into cell lines in order to study the binding properties of 18F-E2. This project will extend our previous work in that we will generate transfected cell lines expressing various mutant or splice variants of ER and will characterise the binding of 18F-E2. This in turn will inform future clinical trials using 18F-E2 to predict cancer behaviour, the effects of differential ER subtype signalling, and the probability that various drugs working through this system may have beneficial anticancer effects.
|Effective start/end date||1/01/17 → 31/12/17|