[18F]3F4AP Imaging for Brain Conditions

Overseen By Marc Normandin, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Massachusetts General Hospital

Disqualifiers: Pregnancy, Breastfeeding, Others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a new imaging agent, F18-3F4AP, can aid in diagnosing brain conditions like traumatic brain injury (TBI) and neurodegenerative diseases such as Alzheimer's. The main goal is to determine the safety of this imaging agent and its behavior in the body, particularly in the brain. The trial also aims to compare images from this new method with traditional MRI scans to assess if it can better highlight brain damage. Suitable participants include those who have experienced TBI or are dealing with memory issues related to Alzheimer's or mild cognitive impairment. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new imaging agent.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that [18F]3F4AP is safe for imaging brain conditions?

Research has shown that [18F]3F4AP is generally safe for humans. One study on its use as a PET tracer for brain conditions found no major safety issues or side effects, indicating it is well-tolerated. This tracer helps image areas of the brain where the protective layer of nerve cells, called myelin, is damaged. Notably, [18F]3F4AP is based on a compound used in an approved treatment for multiple sclerosis, which adds reassurance about its safety. Additionally, studies on its distribution in the body and radiation exposure have shown that the radiation levels are safe. Overall, these findings support the safety of [18F]3F4AP for imaging purposes. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about [18F]3F4AP imaging because it offers a novel way to visualize brain conditions like traumatic brain injury and Alzheimer's disease, potentially improving diagnosis and monitoring. Unlike current imaging techniques that provide only structural information, [18F]3F4AP targets and highlights areas of the brain where demyelination—a key factor in these conditions—occurs. This method allows for a more precise understanding of the brain's functional state, which could lead to earlier and more accurate intervention.

What evidence suggests that [18F]3F4AP imaging is effective for brain conditions?

Research has shown that [18F]3F4AP is a promising tool for imaging brain conditions like traumatic brain injury (TBI) and diseases such as mild cognitive impairment (MCI) and Alzheimer's Disease (AD). The trial will include various treatment arms, focusing on TBI and AD/MCI, to evaluate the effectiveness of [18F]3F4AP in these conditions. This PET radiotracer targets specific brain channels and has effectively identified damaged areas in the brain, known as demyelinated lesions. In studies with animals and some human cases, [18F]3F4AP successfully highlighted these lesions, indicating its potential for improved diagnosis and monitoring. Although detailed human data remains limited, early findings support its ability to map areas of brain injury and disease. This could help doctors better understand and track the progression of these conditions. ^{1 3 6 7 8}

Who Is on the Research Team?

Marc Normandin, PhD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for adults over 18, except those with Alzheimer's who should be aged 60-90. It's not suitable for pregnant or breastfeeding women, anyone trying to get pregnant, or individuals ineligible for PET/CT or MRI studies.

Exclusion Criteria

I am not pregnant, trying to get pregnant, or breastfeeding.

A subject will not be eligible for inclusion in this study if any of the exclusion criteria for PET/CT or MRI studies applies

A negative STAT quantitative serum hCG pregnancy test is required on the day of the PET/CT scan before female subjects of childbearing potential can participate

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety and Dosimetry Assessment

Assess the safety of [18F]3F4AP and radiation doses to main organs in healthy volunteers and subjects with TBI and neurocognitive impairment

8 weeks

Multiple visits for imaging and safety assessments

Pharmacokinetics and Imaging Correlation

Assess pharmacokinetics of [18F]3F4AP and correlate MR images with PET images

12 weeks

Regular imaging sessions and neuropsychological testing

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• F18-3F4AP

Trial Overview [18F]3F4AP is being tested to see if it can help image brain conditions like traumatic brain injury and neurodegenerative diseases. The study will check its safety, radiation doses in organs, how the body processes it, and compare imaging results with neuropsychological tests.

How Is the Trial Designed?

Group I: Traumatic Brain Injury Experimental Treatment 1 Intervention

Group II: Safety/Dosimetry Cohort Experimental Treatment 1 Intervention

Group III: AD/MCI Experimental Treatment 1 Intervention

Group IV: Healthy Controls Active Control 1 Intervention

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Published Research Related to This Trial

The preclinical studies showed that [18F]MK-6240 is safe for use, with no adverse effects observed in rats at doses up to 1000 times the anticipated clinical dose, indicating a strong safety profile for human use.

In human studies, [18F]MK-6240 demonstrated effective biodistribution for brain imaging, with a low effective dose of 5.4 mSv per scan, allowing for multiple imaging sessions per year without significant risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Safety Evaluation and Human Dosimetry of [18F]MK-6240, a Novel PET Tracer for Imaging Neurofibrillary Tangles. Koole, M., Lohith, TG., Valentine, JL., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04710550

NCT04710550 | Exploring the Utility of [18F]3F4AP for ... The overall objective is to obtain an initial assessment of the value of using [18F]3F4AP for imaging demyelinating diseases such as traumatic brain injury (TBI) ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8221756/

Evaluation of the potassium channel tracer [18F]3F4AP in ... Here, we investigate the properties of the K+ channel PET tracer [F]3F4AP in primates and its sensitivity to a focal brain injury that occurred three years ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04699747?tab=table

Investigating the Utility of Demyelination Tracer [18F] ... Aim 4) Correlate MR brain images with [18F]3F4AP PET brain images. Hypothesis 4A: all the lesions seen on the MRI will show increased signal (VT or SUV) on the ...

4. jnm.snmjournals.org jnm.snmjournals.org/content/66/2/293

Imaging Demyelinated Axons After Spinal Cord Injuries with ... Conclusion: [18F]3F4AP demonstrates efficacy in detecting incomplete SCI in both animal models and humans. The potential for monitoring post ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9816249/

Human biodistribution and radiation dosimetry of the ... 18 F 3F4AP is a novel PET radiotracer that targets voltage-gated potassium (K + ) channels and has shown promise for imaging demyelinated lesions.

6. jnm.snmjournals.org jnm.snmjournals.org/content/57/supplement_2/291

[18F]3F4AP: a new PET tracer for brain demyelination We have developed the first PET tracer whose binding increases in demyelinated brain regions. [18F]3F4AP is metabolically stable and is based on an approved MS ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36197499/

Human biodistribution and radiation dosimetry of ... - PubMed No substantial changes in safety assessments or adverse events were recorded. Conclusion: The biodistribution and radiation dosimetry of [18F]3F4AP in humans ...

8. jnm.snmjournals.org jnm.snmjournals.org/content/66/supplement_1/251660

The EPSMS Study: A Multiple Sclerosis Clinical Trial in Progress This study aims to assess the differences in uptake of the radiotracer F18-florbetapir in demyelinated and remyelinated white matter between MS ...