Quantitative non-invasive measurement of estrogen receptor status and receptor availability of the myocardium with positron emission tomography (PET) using 16α-[18F]Fluorestradiol-17β (FES).
Project management at the University of Würzburg:
Cardiovascular diseases remain the leading cause of death in postmenopausal women. For many years, it appeared that estrogen replacement could be a treatment to prevent this disease. However recent epidemiological and experimental data have shown inconsistant results. According to the current literature estrogen replacement seems to have beneficial as well as harmful effects. In addition it must be differentiated between E2 effects mediated by the vasculature and by the myocardium. The investigation of these effects needs the consideration not only of estradiol levels in the blood but also of the distribution of estrogen receptors in target tissues. The first point is easy to do; however methods to measure the receptor status of the human myocardium in vivo are currently not available. The knowledge of the receptor distribution would allow more insights into possible targets of estrogenes.In addition it would improve the dosage of a replacement treatment by measuring free binding sites. In fact it could be shown that estrogen receptors are present in the myocardium. However, these data are exemplary and no data about estrogen receptor status and free binding sites in vivo are available in humans. The development of non-invasive procedures measuring estrogen receptors and free binding sites in vivo is the aim of this project. This will be achieved by using positron emission tomography (PET). The synthesis and labeling of 16α-[18F]Fluorestradiol-17β is known from the literature. This PET-tracer binds specifically to estrogen receptors as demonstrated in meningeomas. After synthesis of 16α-[18F]Fluorestradiol-17β first studies will be performed in perfused isolated rat hearts followed by in-vivo measurements of rats in a PET-scanner designed for small animals. These PET-measurements will deliver time-activity curves used for the development and evaluation of kinetic compartment models. These models will be designed to measure quantitatively association and dissociation of estrogen from the receptor. The next step will be the transfer of the techniques from animal studies to humans. The special impact of the project is the creation of a tool giving more insight into the effectiveness of hormone replacement treatment in humans. The other “estrogen research groups” of Dr. Pelzer, Prof. Dr. Neyses and Dr. Lange will benefit from the tool because animal experiments will be possible under in-vivo conditions. In addition, the study will facilitate the transfer of results from animal experiments to humans.
Projekt period: from 05.2002 to 04.2004