PET Imaging of the Kappa Opioid Receptor in Humans
What is the purpose of this trial?
The kappa opioid receptors (KOR) have been implicated in a number of psychiatric and neurological disorders including depression and related mood disorders, anxiety and stress-related disorders, and Alzheimer's disease. Further, multiple lines of evidence have pointed to the critical role of KOR in dependence symptoms including cocaine, heroin, opiates, nicotine and alcohol dependence. The availability of kappa-selective PET radiotracers will provide the biomedical research community with non-invasive imaging biomarkers to interrogate the kappa opioid receptor in vivo and help gain insights into the function and dysfunction of this receptor system in these disorders. We have developed and carried out the initial evaluation of two KOR selective tracers, one agonist and one antagonist, in non-human primates and humans. Building upon these preliminary data, our first goal is to fully validate the selective KOR agonist radiotracer [11C]GR103545 and the selective antagonist tracer [11C]LY2795050 for PET imaging applications in humans. The second major goal of this project is to use the validated KOR-selective imaging agents to investigate sex and age differences in regional total KOR expression, and the availability of KOR configured in its functional state. The study of sex differences is an important, but relatively new area of research. Recent imaging investigation of the mu opioid receptor indicated strong regional differences between the sexes. Given the sometime synergistic, sometime opposing roles of mu and kappa opioid receptors in vivo, it is important to investigate whether sex also plays a role in KOR expression, or functional state. Such an investigation will provide further insights into future research of sex differences in psychiatric conditions. In addition, we propose to assess the effect of age on KOR, and probe the interactive effects of age and sex.
- 18 Years - 70 Years
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- National Institute of Mental Health
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