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Imaging Biomarkers of Neuroplasticity and Neurodegeneration in the Living Human Brain

Phase 1
Conditions
Normal Healthy Adults
Interventions
Radiation: [18F] TRACK
Device: Measurement of Arterial Input Function
Registration Number
NCT05427656
Lead Sponsor
Thiel, Alexander, M.D.
Brief Summary

Following our recently completed whole body dosimetry study for \[18F\] TRACK in 6 healthy control subjects, the objective of this project is to evaluate brain uptake, regional distribution and in vivo pharmacokinetics for \[18F\] TRACK in 30 cognitively healthy controls using dynamic PET imaging. Specifically, we will evaluate \[18F\] TRACK in three cohorts of healthy control subjects of different ages and both sexes to further explore tracer kinetics in vivo and to determine the most appropriate and robust model to estimate tracer binding to TrkB/C. This will assess normal TrkB/C density in vivo and provide normative data for future use of these tracers in patients.

Detailed Description

We propose to use the radiotracer \[18F\] TRACK to non-invasively image the concentration of TrkB/C in the living human brain with Positron Emission Tomography in 3 different age cohorts. The different subgroups of healthy controls will be used to define the best quantification method for our TrkB/C ligands and to assess a possible age dependency of TrkB/C binding in the healthy population, that may be of particular importance for the future study of patients with Alzheimer's Disearse or mild cognitive impairment. We expect the proposed study to result in 1) a non-invasive method to quantify TrkB/C receptor binding in vivo, 2) age-specific norms of TrkB/C concentration and 3) a simplified approach for quantification which best approximates the full model without the need for arterial blood sampling for future use in patients.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
30
Inclusion Criteria

In order to be considered a healthy control, participants will have a Clinical Dementia Rating (CDR) of 0, Montreal Cognitive Assessment (MoCA) greater than or equal to 26 and Mini-Mental State Exam (MMSE) of 24 or greater, with normal results on the Logical Memory 2 score from the Wechsler Memory Scale-Revise (cut-offs adjusted by education level), and normal scores on the Jessen questions for subjective memory complaints [21]. For the arterial catheter insertion, participants must have two viable arteries of the hand/arm. Women of childbearing potential must undergo a urine pregnancy test and may only be included if the urine pregnancy test is negative.

Exclusion Criteria

Exclusion Criteria: When screening participants, we will question them as to whether they have participated in any other research studies over the past year in which they would have been exposed to radiation. Should they indicate that they have, we would not include them into the present study. A detailed questionnaire regarding Magnetic Resonance Imaging contraindications will be completed with each participant. Should they have any of the following, they will be excluded: cardiac pacemaker, an aneurysm clip, a metal prosthesis (e.g. artificial joints), an artificial heart valve or a metal clip on a blood vessel, metal in the eye or body, tattoos, body piercings, transdermal delivery systems (e.g. patch) or if they suffer from acute claustrophobia. Participants with any psychiatric or neurological conditions that could affect the brain will not be allowed to participate.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
185 MBq [18F] TRACK[18F] TRACKEach participant will receive a single scan with 185 MBq \[18F\] TRACK
185 MBq [18F] TRACKMeasurement of Arterial Input FunctionEach participant will receive a single scan with 185 MBq \[18F\] TRACK
Primary Outcome Measures
NameTimeMethod
Non-invasive method to quantify TrkB/C receptor binding in vivoOne Year

Non-invasive method to quantify TrkB/C receptor binding in vivo

Age-specific norms of TrkB/C concentrationOne Year

Age-specific norms of TrkB/C concentration

Secondary Outcome Measures
NameTimeMethod
Arterial Input Function with Non-Invasive Detector2 months

A simplified approach for quantification which best approximates the full model without the need for arterial blood sampling for future use in patients.

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