PET Imaging of P-glycoprotein Function Using [11C]dLop

NCT00605254 | Completed

• 2 other identifiers: 08006208-M-0062
• Study Type: observational
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

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:

• Electrocardiogram (ECG): A test of the electrical function of the heart.
• Brain PET scans: PET imaging uses small amounts of a radioactive chemical called a tracer that labels active areas of the brain so the activity can be seen with a special camera. The tracer used in this study is \[18F\]FMPEP-d(2). Before starting the scan, a catheter (plastic tube) is placed in a vein in the arm to inject the tracer and another catheter is placed in an artery in the wrist to obtain blood samples during the scan. For the procedure, the subject lies on the scanner bed. A special mask is fitted to the head and attached to the bed to help keep the person s head still during the scan so the images will be clear. A brief scan is done just before the tracer is injected to provide measures of the brain that are helpful in calculating information from subsequent scans. After the tracer is injected, pictures are taken for about 2.5 hours, while the subject lies still on the scanner bed. Blood and urine tests are done after 24 hours after the scan.
• Magnetic resonance imaging (MRI): An MRI scan is done within 1 year (before or after) of the PET scan. This procedure uses a magnetic field and radio waves to produce images of the brain. The subject lies on a table that is moved into the scanner (a tube-like device), wearing earplugs to muffle the noise of the machine during the scanning process. The test takes about 1 hour....

Conditions

Healthy

Keywords

P-Glycoprotein; Positron Emission Tomography; Blood Brain Barrier; Quantitative Imaging; Multi-Drug Transporter; Healthy Volunteer; HV

Outcome Measures

Primary Outcomes (1)

• PET

  continuous

Eligibility Criteria

• Age: 18 Years - 51 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Patients with the diagnosis of probable Alzheimer disease. All patients must meet capacity criteria to consent to research (see Consent documents and process).
• Healthy volunteers.

You may not qualify if:

• Current psychiatric disease, illicit substance use, or severe systemic disease based on history and physical exam.
• Laboratory tests with clinically significant abnormalities. Normal organ and marrow function are defined as: total leukocyte count greater than or equal to 3000 cells/ul, ANC greater than or equal to 1500 cells/ul, platelet count greater than or equal to 100,000 cells/ul, serum creatinine less than or equal to 2.0 times the upper limit of normal, and bilirubin less than or equal to 1.5 times the upper limit of normal, hemoglobin 9.0 g/dL , serum calcium less than or equal to 12.0 mg/dL, AST/ALT less than or equal to 1.5 times the upper limit of normal, PT less than or equal to 1.5 times the upper limit of normal.
• Prior participation in other research protocols or clinical care in the last year such that radiation exposure including that from this protocol would exceed the guidelines set by the Radiation Safety Committee (RSC).
• Pregnancy or breast feeding.
• Positive HIV test.
• Positive result on urine screen for illicit drugs.
• You cannot lie on your back for extended periods of time.
• Use of blood-thinning medications (such as warfarin; aspirin is allowed), current or prior history of coagulopathy. This will be necessary only for subjects who have arterial catheter placement.
• History of neurological disease other than Alzheimer disease.
• For oral tariquidar dose-escalation study: Subjects taking medications other than birth control pills.
• For Alzheimer s disease patients and age-matched volunteers: Subjects taking medications that are known substrates of P-gp that cannot be safely discontinued for this study.

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Awouters F, Niemegeers CJ, Janssen PA. Pharmacology of antidiarrheal drugs. Annu Rev Pharmacol Toxicol. 1983;23:279-301. doi: 10.1146/annurev.pa.23.040183.001431. No abstract available.

  PMID: 6307123 BACKGROUND

• Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna M, Panov AV, Greenamyre JT. Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nat Neurosci. 2000 Dec;3(12):1301-6. doi: 10.1038/81834.

  PMID: 11100151 BACKGROUND

• Bigott HM, Prior JL, Piwnica-Worms DR, Welch MJ. Imaging multidrug resistance P-glycoprotein transport function using microPET with technetium-94m-sestamibi. Mol Imaging. 2005 Jan-Mar;4(1):30-9. doi: 10.1162/15353500200504166.

  PMID: 15967124 BACKGROUND

• Kreisl WC, Bhatia R, Morse CL, Woock AE, Zoghbi SS, Shetty HU, Pike VW, Innis RB. Increased permeability-glycoprotein inhibition at the human blood-brain barrier can be safely achieved by performing PET during peak plasma concentrations of tariquidar. J Nucl Med. 2015 Jan;56(1):82-7. doi: 10.2967/jnumed.114.146894. Epub 2014 Dec 11.

  PMID: 25500831 DERIVED

Study Officials

• William C Kreisl, M.D.

  National Institute of Mental Health (NIMH)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CROSSOVER
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH

Study Record Dates

• First Submitted: January 26, 2008
• First Posted: January 31, 2008
• Study Start: January 24, 2008
• Study Completion: September 4, 2014
• Last Updated: December 17, 2019

Record last verified: 2014-09-04

Locations

US (1)