(18F)-FEPPA PET/MRI Imaging for Frontotemporal Dementia

Overseen By S Jesso, BA

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Must not be taking: Anticoagulation therapy

Disqualifiers: Major depression, Bipolar, Schizophrenia, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial focuses on understanding frontotemporal dementia (FTD) by using advanced imaging to examine brain inflammation and blood flow. A special PET/MRI scan with a marker called (18F)-FEPPA observes the behavior of brain cells involved in inflammation. The researchers aim to identify inflammation patterns linked to different types of FTD. Individuals diagnosed with probable FTD or those without neurological problems who can bring a study partner to clinic visits may be suitable for this trial. As an unphased study, this trial offers a unique opportunity to contribute to groundbreaking research that could enhance the understanding and treatment of FTD.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does prohibit investigational agents (experimental drugs) one month before and during the trial.

What prior data suggests that this imaging technique is safe for evaluating neuroinflammation in frontotemporal dementia?

Research has shown that (18F)-FEPPA is generally safe for people. In studies, it has been used to image certain proteins in the brain without major safety issues. (18F)-FEPPA binds to proteins called activated microglia, which indicate inflammation in the brain. This aids researchers in understanding conditions like frontotemporal dementia.

No serious side effects have been reported in the studies so far. However, it is important to note that this treatment remains under investigation. Researchers continue to gather information on its safety and effectiveness. Overall, current evidence suggests that (18F)-FEPPA is safe for use in imaging studies like this one. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for frontotemporal dementia, which generally focus on managing symptoms with medications like antidepressants and antipsychotics, (18F)-FEPPA offers a new approach by using advanced imaging techniques. This treatment is unique because it involves a PET/MRI scan that targets a specific protein in the brain associated with inflammation, providing detailed insights into the neurological changes occurring in the disease. Researchers are excited about (18F)-FEPPA because it has the potential to enhance early diagnosis and the understanding of disease progression, which could lead to more effective treatments in the future.

What evidence suggests that (18F)-FEPPA PET/MRI imaging is effective for evaluating neuroinflammation in frontotemporal dementia?

Research has shown that the PET tracer FEPPA effectively identifies inflammation in the brain. This is significant because such inflammation is believed to contribute to many brain disorders, including frontotemporal dementia (FTD). In this trial, participants will receive the experimental treatment [18F]FEPPA. Studies have demonstrated that [18F]FEPPA PET scans can detect and display this inflammation by attaching to activated microglia, cells that support the brain's immune system. This ability to highlight brain inflammation could help researchers understand different patterns of the disease and its progression. Although [18F]FEPPA PET is mainly used for research and imaging, early evidence suggests it could be a valuable tool in exploring and understanding FTD. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals diagnosed with probable Frontotemporal Dementia or healthy controls without neurological issues. Participants need a study partner, must be in good health not affecting the study, and women should not be pregnant or of childbearing potential unless properly managed. Exclusions include significant systemic illness, certain medical conditions that affect MRI safety, other major neurologic diseases besides FTD, recent psychiatric disorders, and those exceeding radiation exposure limits.

Inclusion Criteria

Study partner is available who has frequent contact with the subject and can accompany the subject to all clinic visits for the duration of the protocol

I can see and hear well enough for brain function tests.

I am willing to join a year-long imaging study.

Exclusion Criteria

You have received a high amount of radiation from medical procedures in the past year, exceeding the allowed limit set by Health Canada.

My symptoms are not due to a major neurological condition other than possible Frontotemporal Dementia.

You have been diagnosed with schizophrenia according to specific criteria.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neurocognitive Assessment and Imaging

Participants undergo neurocognitive assessment and MRI/PET imaging using the PET ligand FEPPA to evaluate neuroinflammation and cerebral perfusion

1-2 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• (18F)-FEPPA

Trial Overview (18F)-FEPPA PET/MRI imaging is being tested to assess neuroinflammation's role in Frontotemporal Dementia (FTD). The trial involves cognitive assessments and advanced imaging techniques to explore the relationship between brain inflammation, blood flow, and brain structure in patients with different subtypes of FTD.

How Is the Trial Designed?

Group I: (18F)-FEPPA Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

686

Recruited

427,000+

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

678

Recruited

421,000+

London Health Sciences Centre OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

668

Recruited

424,000+

Lawson Health Research Institute

Lead Sponsor

Trials

684

Recruited

432,000+

Published Research Related to This Trial

Frontotemporal dementia is a significant cause of dementia that needs to be differentiated from Alzheimer's disease, highlighting the importance of accurate diagnosis as new treatments are developed.

Structural magnetic resonance imaging (MRI) is currently a valuable tool for distinguishing frontotemporal dementia from Alzheimer's and other non-neurodegenerative diseases, with future research aiming to improve diagnostic methods by examining brain network pathophysiology and protein accumulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frontotemporal dementia neuroimaging: a guide for clinicians. Seeley, WW.[2019]

In a study involving seven patients with semantic variant primary progressive aphasia (svPPA) and 20 controls, all patients showed elevated uptake of the tau PET tracer [18F]Flortaucipir in the anterior temporal lobe, indicating potential tau pathology despite the typical association of svPPA with TDP-43 pathology.

The elevated tracer signal correlated with areas of brain atrophy, suggesting that the tracer may bind to non-tau molecules related to neurodegeneration, highlighting the need for further research to clarify its binding targets in FTLD-TDP cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Flortaucipir tau PET imaging in semantic variant primary progressive aphasia. Makaretz, SJ., Quimby, M., Collins, J., et al.[2021]

The optimized synthesis of the PET biomarker [18F]FEPPA achieved high radiochemical yields (34 ± 2%) and purity (>99%), making it suitable for in vivo studies of neuroinflammation.

In a mouse model, [18F]FEPPA effectively detected increased expression of the translocator protein (TSPO) in response to induced cerebral inflammation, indicating its potential as a reliable biomarker for assessing neuroinflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[18F]FEPPA a TSPO Radioligand: Optimized Radiosynthesis and Evaluation as a PET Radiotracer for Brain Inflammation in a Peripheral LPS-Injected Mouse Model. Vignal, N., Cisternino, S., Rizzo-Padoin, N., et al.[2018]

The study demonstrates that the PET tracer [18F]AV1451 effectively visualizes tau pathology in a patient with frontotemporal dementia (FTD) associated with the V337M MAPT mutation, indicating its potential as a diagnostic tool for this condition.

There is a strong correlation between the degree of [18F]AV1451 binding and the extent of tau pathology and brain atrophy, suggesting that this imaging technique can provide valuable insights into the progression of tau-related neurodegenerative diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frontotemporal dementia with the V337M MAPT mutation: Tau-PET and pathology correlations. Spina, S., Schonhaut, DR., Boeve, BF., et al.[2022]

In a study of 143 participants with confirmed frontotemporal lobar degeneration (FTLD) and varying levels of Alzheimer disease neuropathologic changes (ADNC), FTLD showed significantly higher baseline flortaucipir PET uptake in specific brain regions compared to both high and low ADNC cases.

The study found that baseline flortaucipir uptake was more effective than longitudinal changes in differentiating FTLD from ADNC, with a specific midbrain/inferior temporal uptake ratio providing excellent sensitivity (94%) and specificity (95%) for diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimum Differentiation of Frontotemporal Lobar Degeneration from Alzheimer Disease Achieved with Cross-Sectional Tau Positron Emission Tomography. Josephs, KA., Tosakulwong, N., Gatto, RG., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25655625/

18F-florbetapir PET in patients with frontotemporal ... Cortical (18)F-florbetapir uptake is low in most FTD patients, providing good discrimination from AD. However, visual rating of FTD scans was challenging, ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12134464/

Integrating [18F]FEPPA PET Imaging With 12 Clinical ... This multiyear study aimed to investigate the relationship between TSPO expression and cognitive decline in Alzheimer disease (AD) using 18 F FEPPA PET imaging.

3. clinicalimagingscience.org clinicalimagingscience.org/semantic-dementia-diagnosed-by-f-18-fdg-pet-mri-co-registered-images/

Semantic Dementia Diagnosed by F-18 FDG PET/MRI We present a case where hybrid imaging of PET/MRI was used to diagnose a patient with semantic dementia (SD), which is one of the lesser known subtypes of ...

4. researchgate.net researchgate.net/publication/230678721_Whole_Body_Biodistribution_and_Radiation_Dosimetry_in_Humans_of_a_New_PET_Ligand_18F-FEPPA_to_Image_Translocator_Protein_18_kDa

FEPPA, to Image Translocator Protein (18 kDa) Conclusion: These findings reveal that [18F]FEPPA PET is an effective ... Mapping neuroinflammation in frontotemporal dementia with molecular PET ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6333719/

Dual-phase [18F]florbetapir in frontotemporal dementia Several studies demonstrated that the early phase distribution of [18F]-labeled amyloid tracers, including [18F]florbetapir, show similar patterns as FDG-PET in ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01890343

Imaging Characteristics of Florbetapir 18F in Patients With ... Study 18F-AV-45-010 is designed to evaluate the cerebral uptake of florbetapir 18F as measured by PET imaging in frontotemporal disorder (FTD) ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04720001

NCT04720001 | Florbetaben PET Imaging in PPA Florbetaben F18 is a PET amyloid imaging agent approved by the United States Food and Drug Administration (FDA) to estimate the amount of beta-amyloid plaque in ...