Neva Lazarous (NIMH)
Robert Innis (NIMH)
Sami Zoghbi (NIMH)
Radiotracer studies in human subjects are in progress. Longer-lived versions of the radiotracers are in development.
This invention offers technology to help treat certain brain diseases, such as Alzheimer's disease and Parkinson's, and may lead to more effective and personalized treatments. P-glycoprotein transporter (P-gp) acts as a pump at the blood-brain barrier to exclude a wide range of xenobiotics (e.g., toxins, drugs, etc.) from the brain and is also expressed in a tumor in response to exposure to established/prospective chemotherapeutics (a phenomenon known as multidrug resistance; MDR). The instant invention relates to compounds that are avid substrates for P-gp, and their preparation and use as radiotracers for imaging P-gp function in vitro and in vivo.
- These radiotracers have potential application for investigating the function of P-gp at the blood-brain barrier for human subjects and patients in relation to neuropsychiatric disorders and in cancer. Their application may lead to a better general understanding of the role of P-gp in the unfolding of certain brain diseases (e.g. Alzheimer's disease, Parkinson's disease), and ultimately to more effective and personalized treatment. Likewise, these radiotracers may be applied in oncology to help understand MDR and its clinical manifestation, and to help seek out cancer therapies that avoid MDR.
- This class of radiotracer, typified by the described [11C]dLop, is designed to restrict the formation of radiometabolites that would obstruct the measurement of P-gp function at the blood-brain barrier or at tumors. In this sense these radiotracers are vastly superior to progenitors (e.g. [11C]verapamil, [11C]loperamide), which can only give qualitative not quantitative information.