Exploring the Utility of [18F]3F4AP for Demyelination Imaging

Phase 1

Recruiting

• Conditions: Demyelinating Disorders; Alzheimer's Disease (AD); MS (Multiple Sclerosis); SCI - Spinal Cord Injury; Spinal Radiculopathy; MCI
• Interventions: Drug: [ 18F]3F4AP; Drug: [18F]MK6240; Drug: [11C]PIB

• Registration Number: NCT06999434
• Lead Sponsor: Yale University

Brief Summary

The overall objective is to obtain an assessment of the pharmacokinetics of \[18F\]3F4AP in healthy volunteers and subjects with demyelinating diseases such as mild cognitive impairment (MCI), Alzheimer's Disease (AD), Multiple Sclerosis (MS), Spinal Cord Injury (SCI) and Spinal radiculopathy (SR).

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-05
• Study Start: 2025-05-05
• Study First Submitted: 2025-05-15
• Study First Submitted QC: 2025-05-22
• Last Update Submitted: 2025-05-22
• Study First Posted: 2025-05-31
• Last Update Posted: 2025-05-31
• Primary Completion: 2030-05-05
• Study Completion: 2030-05-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 105

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Healthy Control	[18F]MK6240	n = 30 - up to three PET scanning sessions.
Healthy Control	[11C]PIB	n = 30 - up to three PET scanning sessions.
Alzheimer's Disease (AD)	[ 18F]3F4AP	n = 15 - up to three PET scanning sessions.
Alzheimer's Disease (AD)	[18F]MK6240	n = 15 - up to three PET scanning sessions.
Alzheimer's Disease (AD)	[11C]PIB	n = 15 - up to three PET scanning sessions.
Mild Cognitive Impairment (MCI)	[ 18F]3F4AP	n = 15 - up to three PET scanning sessions.
Mild Cognitive Impairment (MCI)	[18F]MK6240	n = 15 - up to three PET scanning sessions.
Mild Cognitive Impairment (MCI)	[11C]PIB	n = 15 - up to three PET scanning sessions.
Multiple Sclerosis (MS)	[ 18F]3F4AP	n = 15 - up to three PET scanning sessions.
Multiple Sclerosis (MS)	[18F]MK6240	n = 15 - up to three PET scanning sessions.
Multiple Sclerosis (MS)	[11C]PIB	n = 15 - up to three PET scanning sessions.
Spinal Cord Injury (SCI)	[ 18F]3F4AP	n = 15 - up to three PET scanning sessions.
Spinal Cord Injury (SCI)	[18F]MK6240	n = 15 - up to three PET scanning sessions.
Spinal Cord Injury (SCI)	[11C]PIB	n = 15 - up to three PET scanning sessions.
Spinal radiculopathy (SR)	[ 18F]3F4AP	n = 15 - up to three PET scanning sessions.
Spinal radiculopathy (SR)	[18F]MK6240	n = 15 - up to three PET scanning sessions.
Spinal radiculopathy (SR)	[11C]PIB	n = 15 - up to three PET scanning sessions.
Healthy Control	[ 18F]3F4AP	n = 30 - up to three PET scanning sessions.

Primary Outcome Measures

Name	Time	Method
Tau burden	5 years	\[18F\]MK6240 will be used to measure Tau burden.
Tracers volume of distribution (VT)	5 years	PET images measured with \[ 18F\]3F4AP will quantify demyelination, those obtained with \[18F\]MK6240 will quantify tau burden and those obtained with \[11C\]PiB will reflect amyloid burden.; PET images acquired with \[18F\]3F4AP, \[18F\]MK6240 and \[11C\]PiB, will measure the tracers volume of distribution (VT).
Demyelination	5 years	\[18F\]3F4AP will be used to measure demyelination. On the MR images, after co-registration and alignment, signal from pre- and post-contrast T1-weighted images, T2-weighted image, ratio between T1- and T2-weighted images (T1/T2) will be calculated to assess demyelination and white matter lesion (WML) on MR sequences.
Amyloid burden	5 years	\[11C\]PiB will reflect amyloid burden.
Tracer rate constant	5 years	The tracer rate constant for transfer from arterial plasma to tissue K1 and relative delivery R1 will also be estimated using tracer kineticmodeling technique, to provide measures of cerebral perfusion or CBF.
Associations between imaging modalities and biomarkers.	5 years	The Pearson correlation coefficient r will be used to assess the strength of the linear correlations between outcome measures. A P value of 0.05 or less will be considered statistically significant.
Distribution volume ratio (DVR)	5 years	PET images acquired with \[18F\]3F4AP, \[18F\]MK6240 and \[11C\]PiB, will measure the tracers distribution volume ratio (DVR).
Binding potential (BPND)	5 years	PET images acquired with \[18F\]3F4AP, \[18F\]MK6240 and \[11C\]PiB, will measure the tracers binding potential (BPND).

Secondary Outcome Measures

Name	Time	Method
Measure of brain atrophy	5 years	T1 images segmented and parcellated using FreeSurfer will be used to calculate cortical volumes, including the total cortical volume but also the hippocampal volume and will serve as proxies for neocortical and allocortical atrophy.
Measure of cerebrovascular burden	5 years	volume of White matter hyperintensities (WMH) on T1 images or T2 images
Measure of White matter lesions (WML)	5 years	The total WML load score will be calculated as the sum of the frequency of lesions multiplied by their volume.
MR/MRSI images	5 years	Evaluated to determine the effect of pulse sequence parameters and/or hardware configuration on image quality. The images acquired with different pulse sequence parameters or MR hardware configurations will be compared. Comparison of the MR images entails comparing the result of specific image quality measures such as signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) as well as the level of image artifacts

Trial Locations

Locations (1)

Yale University PET Center; 🇺🇸 New Haven, Connecticut, United States