[18F] radiolabeled GnRH antagonist [ (N-(4-((3-fluoropropyl)amino)-2,6-dimethoxyphenyl)-5-((3,8,8-trimethyl- 5,6,7,8-tetrahydronaphthalen-2-yl)methyl)furan-2-carboxamide] as PET imaging agents
To address the feasibility of visualizing GnRH receptors in the central nervous system by micro PET imaging from administration of 18-F GnRH antagonist compund to rats. we will use our own developed [18F] radiolabeled GnRH antagonist [ (N-(4-((3-fluoropropyl)amino -2,6-dimethoxyphenyl)-5-((3,8,8-trimethyl-5,6,7,8-tetrahydronaphthalen- 2-yl)methyl)furan-2-carboxamide]. We will study brain uptake and the pharmacokinetics of the [18F] radiolabeled
GnRH Antagonist in animals. The outcome of our study will evaluate the effectiveness of [18F] radiolabeled GnRH antagonist as powerful preclinical tool in neuroimaging and CNS drug development. Gonadotropin-releasing hormone (GnRH), also known as luteinizing hormone- releasing hormone is a decapeptide that plays an important role in human reproduction. However, there are reports that GnRH has effects in nonreproductive tissues, forcing us to reconsider the role of GnRH in the physiology of living beings. The hippocampus is one of the first brain substructures to be affected in Alzheimer's disease (AD) and expresses high levels of GnRH receptors. In the human hippocampus, pyramidal neurons express GnRH receptors. Similarly, GnRH receptor- immunoreactive neurons were found almost exclusively within the pyramidal cell layer, dentate gyrus, and indusium griseum of the mouse and sheep. Because GnRH is likely to be elevated post-menopause due to the loss of estrogen negative feedback, the effect of GnRH on these neurons may constitute a component of the neurodegenerative pathology that accompanies Alzheimer's disease. Accordingly, diagnostic tools for evaluating GnRH receptor activity in the CNS can provide useful and prognostic valuable information with respect to an individual risk for developing AD.
GnRH Antagonist in animals. The outcome of our study will evaluate the effectiveness of [18F] radiolabeled GnRH antagonist as powerful preclinical tool in neuroimaging and CNS drug development. Gonadotropin-releasing hormone (GnRH), also known as luteinizing hormone- releasing hormone is a decapeptide that plays an important role in human reproduction. However, there are reports that GnRH has effects in nonreproductive tissues, forcing us to reconsider the role of GnRH in the physiology of living beings. The hippocampus is one of the first brain substructures to be affected in Alzheimer's disease (AD) and expresses high levels of GnRH receptors. In the human hippocampus, pyramidal neurons express GnRH receptors. Similarly, GnRH receptor- immunoreactive neurons were found almost exclusively within the pyramidal cell layer, dentate gyrus, and indusium griseum of the mouse and sheep. Because GnRH is likely to be elevated post-menopause due to the loss of estrogen negative feedback, the effect of GnRH on these neurons may constitute a component of the neurodegenerative pathology that accompanies Alzheimer's disease. Accordingly, diagnostic tools for evaluating GnRH receptor activity in the CNS can provide useful and prognostic valuable information with respect to an individual risk for developing AD.