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

NCT06999434 | Recruiting Phase 1 FDA Drug

• 5 other identifiers: 20000392827P41EB022544-087R01EB033582-037R01AG076153-031R01AG085561-01
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 1

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).

Conditions

Demyelinating Disorders; MCI; Alzheimer's Disease (AD); MS (Multiple Sclerosis); SCI - Spinal Cord Injury; Spinal Radiculopathy

Keywords

3F4AP; Demyelinating Disorders; MS; SCI; AD

Outcome Measures

Primary Outcomes (8)

• Tracers volume of distribution (VT)

  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).

  5 years

• Distribution volume ratio (DVR)

  PET images acquired with \[18F\]3F4AP, \[18F\]MK6240 and \[11C\]PiB, will measure the tracers distribution volume ratio (DVR).

  5 years

• Binding potential (BPND)

  PET images acquired with \[18F\]3F4AP, \[18F\]MK6240 and \[11C\]PiB, will measure the tracers binding potential (BPND).

  5 years

• Demyelination

  \[18F\]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.

  5 years

• Tau burden

  \[18F\]MK6240 will be used to measure Tau burden.

  5 years

• Amyloid burden

  \[11C\]PiB will reflect amyloid burden.

  5 years

• Tracer rate constant

  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.

  5 years

• Associations between imaging modalities and biomarkers.

  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.

  5 years

Secondary Outcomes (4)

• Measure of brain atrophy

  5 years

• Measure of cerebrovascular burden

  5 years

• Measure of White matter lesions (WML)

  5 years

• MR/MRSI images

  5 years

Study Arms (6)

Healthy Control

ACTIVE COMPARATOR

n = 30 - up to three PET scanning sessions.

Drug: [ 18F]3F4AP; Drug: [18F]MK6240; Drug: [11C]PIB

Alzheimer's Disease (AD)

EXPERIMENTAL

n = 15 - up to three PET scanning sessions.

Drug: [ 18F]3F4AP; Drug: [18F]MK6240; Drug: [11C]PIB

Mild Cognitive Impairment (MCI)

EXPERIMENTAL

n = 15 - up to three PET scanning sessions.

Drug: [ 18F]3F4AP; Drug: [18F]MK6240; Drug: [11C]PIB

Multiple Sclerosis (MS)

EXPERIMENTAL

n = 15 - up to three PET scanning sessions.

Drug: [ 18F]3F4AP; Drug: [18F]MK6240; Drug: [11C]PIB

Spinal Cord Injury (SCI)

EXPERIMENTAL

n = 15 - up to three PET scanning sessions.

Drug: [ 18F]3F4AP; Drug: [18F]MK6240; Drug: [11C]PIB

Spinal radiculopathy (SR)

EXPERIMENTAL

n = 15 - up to three PET scanning sessions.

Drug: [ 18F]3F4AP; Drug: [18F]MK6240; Drug: [11C]PIB

Interventions

[ 18F]3F4AP DRUG

PET Scan #3

Alzheimer's Disease (AD); Healthy Control; Mild Cognitive Impairment (MCI); Multiple Sclerosis (MS); Spinal Cord Injury (SCI); Spinal radiculopathy (SR)

[18F]MK6240 DRUG

PET Scan #2

Alzheimer's Disease (AD); Healthy Control; Mild Cognitive Impairment (MCI); Multiple Sclerosis (MS); Spinal Cord Injury (SCI); Spinal radiculopathy (SR)

[11C]PIB DRUG

PET Scan #1

Alzheimer's Disease (AD); Healthy Control; Mild Cognitive Impairment (MCI); Multiple Sclerosis (MS); Spinal Cord Injury (SCI); Spinal radiculopathy (SR)

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and Female subjects must be ≥18 and \<90 years of age;
• Able to understand and provide informed consent prior to study procedures
• Must be in good health

You may not qualify if:

• Less than 18 years of age;
• Pregnant or breastfeeding;
• Any significant systemic illness or unstable medical condition;
• Pre-existing medical conditions or claustrophobic reactions;
• Research-related radiation exposure exceeds current PET Center guidelines (i.e. 50 mSv in the prior 12 months);
• History of a bleeding disorder or are currently taking anticoagulants.

Sponsors & Collaborators

• Yale University: lead
• National Institute for Biomedical Imaging and Bioengineering (NIBIB): collaborator
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Yale University PET Center

New Haven, Connecticut, 06510, United States

RECRUITING

MeSH Terms

Conditions

Demyelinating Diseases; Alzheimer Disease; Multiple Sclerosis; Spinal Cord Injuries

Interventions

2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole

Condition Hierarchy (Ancestors)

Nervous System Diseases; Dementia; Brain Diseases; Central Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Autoimmune Diseases; Immune System Diseases; Spinal Cord Diseases; Trauma, Nervous System; Wounds and Injuries

Study Officials

• Georges El Fakhri, PhD, DABR

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shannan Henry

CONTACT

+1 (203) 737-5278; shannan.henry@yale.edu

Kayla Cottiers

CONTACT

203-737-7496; kayla.cottiers@yale.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Radiology and Biomedical Imaging and of Biomedical Informatics & Data Science

Study Record Dates

• First Submitted: May 15, 2025
• First Posted: May 31, 2025
• Study Start: May 5, 2025
• Primary Completion (Estimated): May 5, 2030
• Study Completion (Estimated): May 5, 2030
• Last Updated: May 31, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)