(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

Trial Summary

What is the purpose of this trial?

Neuroinflammation is increasingly implicated as a potential critical pathogenic mechanism in a variety of neurologic and psychiatric disorders. This study will use hybrid PET/MRI imaging to evaluate neuroinflammation and its relationship to cerebral perfusion in frontotemporal dementia (FTD). Patients with FTD will be recruited from the Cognitive Neurology and Aging Brain clinics at Parkwood Institute and will undergo neurocognitive assessment and MRI/PET using the PET ligand FEPPA which binds to activated microglia, a marker of neuroinflammation. Correlations will be conducted to determine whether abnormal neuroinflammation is present in Frontotemporal dementia and whether differential patterns of neuroinflammation are present in different FTD clinical and molecular subtypes, and to determine the relationship between neuroinflammation, cerebral perfusion using arterial spin labeling MRI imaging techniques, and indices of brain structure including volumetric and white matter analysis.

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.

How does the treatment using (18F)-FEPPA PET/MRI imaging differ from other treatments for frontotemporal dementia?

(18F)-FEPPA PET/MRI imaging is unique because it uses a specific radioligand, (18F)-FEPPA, to visualize brain inflammation and glial activation, which are not typically targeted by standard treatments for frontotemporal dementia. This imaging approach helps in assessing neuroinflammation, providing a novel way to understand and potentially monitor the disease. ^{1 2 3 4 5}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

References

1. Switzerland 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. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Optimum Differentiation of Frontotemporal Lobar Degeneration from Alzheimer Disease Achieved with Cross-Sectional Tau Positron Emission Tomography. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

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

4. England pubmed.ncbi.nlm.nih.gov

Flortaucipir tau PET imaging in semantic variant primary progressive aphasia. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Frontotemporal dementia with the V337M MAPT mutation: Tau-PET and pathology correlations. [2022]