F-18 3F4AP Imaging for Multiple Sclerosis

Overseen By Pedro Brugarolas, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Massachusetts General Hospital

Disqualifiers: Brain disease, MRI/PET contraindications, others

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

Compensation: Varies

Number of Visits: 7

Duration: 5 years

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the safety and effectiveness of a new imaging tool, F-18 3F4AP, for people with multiple sclerosis (MS). Researchers will assess how this tool functions in both healthy individuals and those with MS by comparing brain images and examining its interaction with brain activity. Participants may qualify if they have been diagnosed with MS and do not have metal implants or severe claustrophobia, as these conditions can interfere with imaging tests. As a Phase 1 trial, participants will be among the first to help researchers understand how this new imaging tool works in people.

Do I need to stop my current medications for the trial?

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 F-18 3F4AP is safe for imaging in humans?

Research has shown that F-18 3F4AP has been tested for safety in humans, specifically in healthy volunteers. In these studies, researchers examined how the tracer (a substance used in imaging) spreads in the body and the level of radiation exposure it involves. These early findings are important for understanding its effects.

So far, detailed reports of side effects or major changes in vital signs have not emerged after using F-18 3F4AP in these initial studies. This suggests that the tracer is generally well-tolerated. However, since this is a Phase 1 trial, the main goal is to assess safety and gather initial data on how the body processes the tracer. Phase 1 trials are the first step in testing new treatments in humans, usually involving a small number of participants to find the safest dose.

For those considering joining a trial using F-18 3F4AP, this initial safety information might be reassuring. However, participating in any clinical trial is a personal decision that should be made after discussing potential risks and benefits with a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about F-18 3F4AP imaging for multiple sclerosis because it offers a novel way to visualize nerve damage in the brain. Unlike standard MRI scans, which only provide indirect clues about disease activity, F-18 3F4AP PET scans can directly highlight areas of demyelination, the hallmark of multiple sclerosis. This imaging technique could lead to more precise tracking of disease progression and better assessment of treatment effectiveness.

What evidence suggests that F-18 3F4AP is effective for imaging multiple sclerosis?

Research has shown that F-18 3F4AP is a promising tool for imaging multiple sclerosis (MS). One study found that this PET tracer attaches differently to various MS lesions, potentially aiding in identifying damaged brain areas. In animal studies, F-18 3F4AP successfully crossed into the brain and highlighted areas of injury, showing more than twice the attachment in damaged parts. These findings suggest F-18 3F4AP might help visualize and understand the extent of brain damage in MS. Although human studies provide limited information, these early results are encouraging for its use in imaging nerve damage in MS. Participants in this trial will undergo F-18 3F4AP PET scans, with separate arms for healthy controls and those with multiple sclerosis, to further evaluate its effectiveness. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults aged 18 to 65 with or without multiple sclerosis (MS) who can consent to the study. It excludes those with brain diseases like tumors or stroke, MRI/PET contraindications such as metal implants, severe claustrophobia, certain chronic diseases, allergy to contrast agents used in imaging, excessive prior radiation exposure, pregnant or lactating women, and any unstable health conditions.

Inclusion Criteria

I understand the study and can give my consent.

Exclusion Criteria

You have had allergic reactions to Dotarem or other gadolinium contrast agents in the past.

Inability to provide written informed consent

I am not pregnant, breastfeeding, and there's no chance I could be pregnant before starting treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Initial assessment including PET and MRI scans to establish baseline measurements

1 week

1 visit (in-person)

Treatment

Administration of [18F]3F4AP and assessment of safety, pharmacokinetics, and imaging correlation

5 years

Multiple visits (in-person) over 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

1 visit (in-person) for retest

What Are the Treatments Tested in This Trial?

Interventions

• F-18 3F4AP

Trial Overview [18F]3F4AP is being tested for its ability to image demyelination in MS using PET scans. The study will check if it's safe for humans; compare how it moves through the body of healthy people versus those with MS; ensure consistent results on repeated tests; match PET images with MRI findings and correlate them with neuropsychological test scores and disability levels in MS patients.

How Is the Trial Designed?

Group I: Multiple sclerosis Experimental Treatment 1 Intervention

F-18 3F4AP PET Scan

Group II: Healthy controls Active Control 1 Intervention

F-18 3F4AP PET Scan

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Published Research Related to This Trial

Gadolinium-enhanced MRI is crucial for understanding multiple sclerosis (MS) and monitoring disease activity, but its effectiveness can be limited by sensitivity and specificity issues, particularly in detecting low-grade inflammation.

Using a triple dose of gadolinium may improve the detection of MS inflammation, and Gd-enhanced MRI should be part of the initial diagnostic process for patients with early neurological symptoms to predict the progression to clinically definite MS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contrast enhancement and the acute lesion in multiple sclerosis. Rovaris, M., Filippi, M.[2015]

The study presents a new method for producing the PET tracer [18F]3F4AP, which is a radiofluorinated version of the drug 4-aminopyridine, aimed at imaging demyelination in multiple sclerosis.

The production process involves an automated synthesizer and a flow hydrogenation reactor, along with standard quality control measures, paving the way for future clinical applications of this tracer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Automated Radiochemical Synthesis of [18F]3F4AP: A Novel PET Tracer for Imaging Demyelinating Diseases. Brugarolas, P., Bhuiyan, M., Kucharski, A., et al.[2019]

MRI is crucial for diagnosing multiple sclerosis (MS), often confirming the presence and location of lesions suggested by clinical evaluations, and it has largely replaced other diagnostic tests.

Recent advancements in MRI technology may enable quicker imaging and more precise quantification of lesions, which could enhance the evaluation of treatment effectiveness in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple sclerosis: the impact of MR imaging. Wallace, CJ., Seland, TP., Fong, TC.[2015]

The study used hybrid [18F]florbetapir PET-MR imaging to assess myelin damage in 18 relapsing-remitting MS patients, revealing that demyelination occurs not only in visible lesions but also in normal-appearing white matter.

The imaging technique effectively measured in-vivo myelin damage, showing a significant correlation between myelin integrity and diffusion metrics, suggesting its potential utility in clinical management of MS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[18F]Florbetapir PET/MR imaging to assess demyelination in multiple sclerosis. Carotenuto, A., Giordano, B., Dervenoulas, G., et al.[2021]

The PET tracer [18F]3F4AP shows promising properties for imaging demyelination, including high brain penetration and specificity, making it a potential new tool for assessing myelin repair therapies in neurological diseases.

In primate studies, [18F]3F4AP demonstrated greater sensitivity to focal brain injury compared to traditional imaging methods like [18F]FDG and MRI, indicating its effectiveness in detecting changes associated with demyelination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the potassium channel tracer [18F]3F4AP in rhesus macaques. Guehl, NJ., Ramos-Torres, KM., Linnman, C., et al.[2022]

Regular monitoring of multiple sclerosis (MS) using contrast-enhanced brain MRI is crucial for assessing the disease's progression and the effectiveness of disease-modifying therapies, with recommendations for scans at 6-month intervals after starting treatment.

The presence of gadolinium-enhancing lesions or new/enlarging T2 lesions on MRI scans can indicate a suboptimal response to therapy, suggesting that a change in treatment may be necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical applications of imaging disease burden in multiple sclerosis: MRI and advanced imaging techniques. Riley, C., Azevedo, C., Bailey, M., et al.[2022]

The novel PET radiotracer [18F]3F4AP showed a favorable biodistribution in healthy human volunteers, with the highest activity in the kidneys, urinary bladder, stomach, liver, spleen, and brain, and it cleared from circulation faster than in previous animal studies.

The average effective dose of [18F]3F4AP was 12.1 μSv/MBq, which is lower than other fluorine-18 radiotracers, indicating a potentially safer profile for human imaging without any reported adverse events during the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human biodistribution and radiation dosimetry of the demyelination tracer [18F]3F4AP. Brugarolas, P., Wilks, MQ., Noel, J., et al.[2023]

Monthly T2-weighted and gadolinium-enhanced brain MRI is highly effective for detecting disease activity in relapsing-remitting and secondary progressive multiple sclerosis (MS), making it a valuable primary endpoint in short-term clinical trials.

While MRI can indicate pathological changes, it has limited correlation with disability in established MS, so clinical outcomes should remain the primary focus in definitive trials, with MRI serving as a useful secondary measure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Guidelines for the use of magnetic resonance techniques in monitoring the treatment of multiple sclerosis. US National MS Society Task Force. Miller, DH., Albert, PS., Barkhof, F., et al.[2007]

A deep learning model was successfully used to enhance the image quality of accelerated brain MR scans for patients with multiple sclerosis, allowing for faster procedures without significantly compromising the quality of volumetric measurements.

The study found that while there were small differences in volumetric measurements between conventional and deep learning-enhanced fast scans, these differences did not affect the correlation with important patient-reported outcomes related to MS symptoms and disability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Applying Deep Learning to Accelerated Clinical Brain Magnetic Resonance Imaging for Multiple Sclerosis. Mani, A., Santini, T., Puppala, R., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40759830/

First evaluation in multiple sclerosis using PET tracer [18F ... First evaluation in multiple sclerosis using PET tracer [18F]3F4AP demonstrates heterogeneous binding across lesions. Eur J Nucl Med Mol Imaging ...

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

Investigating the Utility of Demyelination Tracer [18F] ... Our overall objective is to obtain an initial assessment of the potential value of using [18F]3F4AP for imaging demyelinating diseases such as multiple ...

3. 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 ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0960894X24003937

Synthesis of K+ channel radioligand [18F]5-methyl-3-fluoro ... PET/CT studies using naïve mice demonstrate that [18F]5Me3F4AP effectively crosses the blood–brain barrier and has comparable kinetics to [18F] ...

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

Imaging Demyelinated Axons After Spinal Cord Injuries with ... Results: [18F]3F4AP PET of SCI rats revealed a more than 2-fold increase in tracer binding highly localized to the injured segment of the ...

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

Human biodistribution and radiation dosimetry of the ... The goal of this study was to assess the biodistribution, radiation dosimetry, and safety of [18F]3F4AP in healthy volunteers. The study ...

7. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/265582

Investigating the Utility of Demyelination Tracer [18F] ... Our overall objective is to obtain an initial assessment of the potential value of using \[18F\]3F4AP for imaging demyelinating diseases such as multiple ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11800733/

Imaging Demyelinated Axons After Spinal Cord Injuries with ... Results: [18F]3F4AP PET of SCI rats revealed a more than 2-fold increase in tracer binding highly localized to the injured segment of the cord ...