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Radiotracers for Imaging P-glycoprotein Transporter Function

Posted Jun 15 2010 5:00pm

Description of Invention:
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.

Development Status:
Radiotracer studies in human subjects are in progress. Longer-lived versions of the radiotracers are in development.

Victor W Pike (NIMH)
Sami S Zoghbi (NIMH)
Neva P Lazarous (NIMH)
Robert B Innis (NIMH)

Patent Status:
HHS, Reference No. E-318-2007/0
US, Application No. 12/112,994 filed 30 Apr 2008

Relevant Publication:
  1. SS Zoghbi, JS Liow, F Yasuno, J Hong, E Tuan, N Lazarova, RL Gladding, VW Pike, RB Innis. 11C-Loperamide and its N-desmethyl radiometabolite are avid substrates for brain P-glycoprotein efflux. J Nucl Med. 2008 Apr;49(4):649-656. [ PubMed abs ]
  2. N Lazarova, SS Zoghbi, J Hong, N Seneca, E Tuan, RL Gladding, JS Liow, A Taku, RB Innis, VW Pike. Synthesis and evaluation of [N-methyl-11C]N-desmethyl-loperamide as a new and improved PET radiotracer for imaging P-gp function. J Med Chem. 2008 Oct 9;51(19):6034-6043. [ PubMed abs ]
  3. JS Liow, W Kreisl, SS Zoghbi, N Lazarova, N Seneca, RL Gladding, A Taku, P Herscovitch, VW Pike, RB Innis. P-glycoprotein function at the blood-brain barrier imaged using 11C-N-desmethyl-loperamide in monkeys. J Nucl Med. 2009 Jan;50(1):108-115. [ PubMed abs ]

Licensing Status:
Available for licensing.

Collaborative Research Opportunity:
The National Institute of Mental Health Molecular Imaging Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize radiotracers for imaging P-gp function. Please contact Victor Pike at for more information.

Devices/Instrumentation - Diagnostics
Devices/Instrumentation - Therapeutics
In-vivo Data
In-vitro Data

For Additional Information Please Contact:
Susan Ano Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Phone: 301-435-5515
Fax: 301-402-0220

Ref No: 1909

Updated: 06/2010

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