PET Imaging of P-glycoprotein Function Using [11C]dLop
|First Received Date ICMJE||January 26, 2008|
|Last Updated Date||March 14, 2014|
|Start Date ICMJE||January 2008|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||To measure P-glycoprotein function in healthy volunteers by performing brain PET imaging studies with [11C]dLop.|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00605254 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||To determine the whole body biodistribution of activity and thereby calculate exposure to organs of the body with [11C]dLop.|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||PET Imaging of P-glycoprotein Function Using [11C]dLop|
|Official Title ICMJE||Brain and Whole Body Imaging of P-Glycoprotein Function Using [11C]dLop|
This study will test the use of a radioactive substance called [11C]dLop for measuring P-glycoprotein (P-gp) using positron emission tomography (PET) imaging. The P-gp protein acts as a pump in cells, affecting a variety of functions, such as limiting drug absorption and elimination and decreasing drug penetration into certain tissues, such as the brain. It is a major obstacle to successful chemotherapy because it can pump cancer drugs out of the cells, interfering with treatment. Decreased P-gp function may contribute to disorders such as Parkinson s disease and Alzheimer s disease, whereas higher levels of the protein have been found in patients with epilepsy and in several forms of drug-resistant cancer tumors. This study will determine uptake and clearance of [11C]dLop and the radiation exposure to organs of the body to assess its possible use in further studies of P-gp function.
Healthy normal volunteers between 18 and 51 years of age may be eligible for this study. Candidates are screened with a medical history, physical examination and blood and urine tests.
Participants undergo the following procedures:
P-glycoprotein (P-gp) is an ATP-binding cassette (ABC) transporter and is the major efflux pump in the blood-brain barrier. P-gp has several physiological roles such as limiting drug absorption, active drug elimination, and limits drug penetration into sensitive tissues (e.g., brain and testis) (Fromm, 2004). Reduced activity or expression of P-gp may contribute to neurodegenerative disorders such as Parkinson s and Alzheimer s disease. The reduced activity of P-gp (i.e., decreased neuroprotection at the blood brain barrier) may allow harmful pesticides access to the brain which can damage the brain s dopaminergic cell groups possibly leading to Parkinson s disease (Betarbet et al., 2000; Kortekaas et al., 2005). The increased deposition of beta-amyloid in Alzheimer s disease, may be due in part, to the decreased elimination of cerebral beta-amyloid in brain (Vogelgesang et al., 2002). Conversely, an overexpression of P-gp has been found in epilepsy and in several forms of multi drug resistant cancer tumors (Brandt et al., 2006; Szakacs et al., 2006). In vivo evaluation of P-gp function in the brain and throughout the body is important in disease states, and in therapeutic and diagnostic drug evaluation.
P-gp function has been assessed in healthy volunteers with positron emission tomography (PET) using [11C]verapamil, nevertheless, accurate quantification of this PET radioligand is difficult due to the large contribution of radiometabolites and low signal (Ikoma et al., 2006; Lee et al., 2006; Lubberink et al., 2007). Therefore, we have recently developed [11C]dLop as an alternative radioligand for imaging P-gp function, which will allow a more accurate quantification of P-gp with a higher signal and less contribution of radiometabolites. In the current protocol, we wish to evaluate [11C]dLop in healthy volunteers to determine the kinetics of brain imaging of P-gp function. In order to simulate P-gp dysfunction in healthy volunteers we will administer the P-gp inhibitor tariquidar. We will perform brain PET scans using [11C]dLop before and after P-gp blockade in order to quantify P-gp function at the blood-brain barrier.
|Study Type ICMJE||Observational|
|Study Design ICMJE||Time Perspective: Prospective|
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Not Provided|
|Study Population||Not Provided|
|Intervention ICMJE||Not Provided|
|Study Group/Cohort (s)||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE||126|
|Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
For the dose escalation study using oral tariquidar, we will select healthy adult female and male volunteers (age 18-51 years old). These healthy volunteers will be medication free, excluding birth control pills. These subjects will be asked to abstain from any medications 16 days before and 1 week after participation in the study.
For the AD study, we will select male and female AD patients and age-matched volunteers who are at least 45 years of age.
|Ages||18 Years to 51 Years|
|Accepts Healthy Volunteers||Yes|
|Location Countries ICMJE||United States|
|NCT Number ICMJE||NCT00605254|
|Other Study ID Numbers ICMJE||080062, 08-M-0062|
|Has Data Monitoring Committee||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Institute of Mental Health (NIMH)|
|Collaborators ICMJE||Not Provided|
|Information Provided By||National Institutes of Health Clinical Center (CC)|
|Verification Date||February 2014|
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