NCT01386476

(18F)FCWAY and the Blood-Brain Barrier

The Serotonin-1A Receptor Radioligand (18F)FCWAY as a Potential Substrate for Efflux Transport at the Blood-Brain Barrier

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 18 (actual)
• Sponsor: National Institute of Mental Health (NIMH) · NIH
• Sex: All
• Age: 18 Years – 50 Years
• Healthy volunteers: Accepted

Summary

Background: \- The blood-brain barrier helps protect the brain from infections and toxins in the blood stream. But it can also prevent certain drugs from reaching the brain to treat diseases or other problems. Researchers are interested in chemicals that will help show how the barrier works. One possible chemical, (18F)FCWAY, may be useful for studying the barrier. More tests are needed to determine how effective it is. Objectives: \- To test whether (18F)FCWAY can be used to help study the blood-brain barrier. Eligibility: \- Healthy volunteers between 18 and 50 years of age. Design: * This study requires a screening visit and two scanning visits. * Participants will be screened with a physical exam and medical history. They will also have blood and urine tests. * At the first scanning visit, participants will have a magnetic resonance imaging scan to provide baseline images of the brain. * Before the second visit, some participants will stay overnight in the hospital. They will receive the drug tariquidar, which may help the (18F)FCWAY show the blood-brain barrier more clearly. * At the second scanning visit, all participants will have a positron emission tomography scan with (18F)FCWAY to see how well the drug shows the blood-brain barrier on the scan.

Detailed description

Objective: We use the radioligand \[(11)C\]dLop (N-desmethyl-loperamide) in positron emission tomography (PET) studies to measure function of P-gp, an efflux transporter at the blood-brain barrier. Because \[(11)C\]dLop is an avid substrate for P-gp, we see almost no radioactivity in brain at baseline in healthy volunteers. However, we do see increased radioactivity in brain in some patients with dementia, or when we co-administer a medication which blocks the function of P-gp. While \[(11)C\]dLop is useful for detecting increased radioactivity in brain, a disadvantage of \[(11)C\]dLop is that it is not useful for detecting decreased radioactivity in brain. The reason for this is that we have a floor effect, where we are unable to detect less radioactivity than zero. Preclinical studies indicate that increases in P-gp activity (which would manifest as decreased radioactivity in brain) correlate with drug-resistant epilepsy and HIV. To better understand diseases associated with not only increased but also decreased P-gp activity, we wish to identify a radioligand which is a moderate substrate of P-gp. We suspect that \[(18)F\]FCWAY is a moderate substrate for P-gp, because some radioligand gets into brain at baseline, but more gets into brain after administering a drug (disulfiram) which inhibits P-gp. The objective of this study is to determine whether the serotonin 1A antagonist \[(18)F\]FCWAY is a substrate of P-gp by determining whether the P-gp inhibitor, tariquidar, increases uptake of the radioligand into brain. Study Population: We will study up to 45 healthy adults, ages 18-50. Participants must be free of medications, with the exception of birth control pills, as medications may confound our data. or iii patients who received a single PET scan as stated under i), will be invited back to have the option of receiving the second PET scan with tariquidar. A maximum of 15 ubjects will receive both scans. Design: Healthy adults will undergo either 1) a single PET scan of the brain with \[(18)F\]FCWAY (at baseline, or during infusion of intravenous tariquidar or 2) two PET scans (both a baseline and a tariquidar scan). Outcome Measures: If \[(18)F\]FCWAY is a substrate of P-gp, pre-treatment with tariquidar will increase its brain uptake of \[(18)F\]FCWAY and delay the time of peak uptake.

Conditions

• Drug Resistance

Timeline

• Start date: 2011-06-15
• Completion: 2016-09-01
• First posted: 2011-07-01
• Last updated: 2018-07-05

Locations

1 site across 1 country: United States