PET Imaging for Fatty Liver Disease

Overseen By Dana Little, MS

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of California, Davis

Must not be taking: Anticoagulants

Disqualifiers: Alcohol abuse, Hepatitis B/C, Neurodegenerative disorders, others

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

Compensation: Varies

Number of Visits: Unknown

12 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on anticoagulant therapy, you cannot participate in the trial.

What data supports the effectiveness of the drug 18F-DPA-714, 18F-FDG, Fluorodeoxyglucose F 18, FDG F 18, Fludeoxyglucose F 18 for fatty liver disease?

The use of FDG PET/CT imaging, which involves Fluorodeoxyglucose F 18, has shown promise in diagnosing inflammatory liver conditions like non-alcoholic steatohepatitis (NASH), a severe form of fatty liver disease. This imaging technique has been successful in other inflammatory diseases, suggesting it could be useful for assessing liver inflammation in fatty liver disease. ^{1 2 3 4 5}

Is PET imaging using 18F-labeled compounds safe for humans?

An acute toxicity study was conducted for the PET radiopharmaceutical [(18)F]FEDAC, which is used for imaging various conditions, including liver diseases, and it is considered safe for clinical use. ^{1 6 7 8 9}

How is the drug 18F-DPA-714, 18F-FDG unique for treating fatty liver disease?

The drug 18F-DPA-714, 18F-FDG is unique for treating fatty liver disease because it uses PET imaging to detect inflammation and mitochondrial dysfunction in the liver, providing a non-invasive way to diagnose and monitor the disease, unlike traditional methods that often require a liver biopsy. ^{4 7 10 11 12}

What is the purpose of this trial?

Alzheimer's Disease and related dementias (ADRD) affect about 6 million people in the U.S. and are the fifth leading cause of death for adults over 65. Recent research is investigating how chronic liver diseases like Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), which affects one-third of the U.S. population, might influence ADRD through the liver-brain axis. MASLD shares risk factors with Alzheimer's, such as diabetes and hypertension, and studies have linked MASLD to increased risks of cognitive decline and ADRD. Mouse-model studies suggest that chronic liver inflammation in MASLD can induce neuroinflammation and accelerate Alzheimer's pathology, highlighting the importance of studying the liver-brain connection to identify new therapeutic targets for ADRD. The goal of this research is to develop a practical PET imaging method using 18F-FDG to simultaneously assess liver and brain inflammation in patients with MASLD-related ADRD. This approach leverages dynamic FDG-PET scanning and advanced tracer kinetic modeling to quantify glucose transport, overcoming limitations of traditional imaging methods that cannot noninvasively assess chronic liver inflammation. The new method aims to enable comprehensive imaging of liver-brain inflammation crosstalk, validated against the 18F-DPA-714 radiotracer. Success in this project could provide a valuable imaging tool for linking liver inflammation with neuroinflammation and cognitive decline, advancing clinical research and potentially uncovering new pathways for ADRD treatment

Research Team

Guobao Wang, PhD

Principal Investigator

UC Davis Health Department of Radiology

Eligibility Criteria

This trial is for adults with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) who may also be experiencing cognitive decline. The study aims to explore the connection between liver inflammation and brain health using advanced PET imaging techniques.

Inclusion Criteria

Ability to provide informed consent

I have had, or will have, a liver biopsy for fatty liver disease within the last 6 months.

Exclusion Criteria

I am not pregnant or breastfeeding.

My body weight is under 225 kg.

I have a history of liver issues, but not due to non-alcoholic fatty liver disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants will undergo positron emission tomography scans with 18F-FDG and 18F-DPA-714 to assess neuroinflammation and liver-brain inflammation crosstalk

3 months

Multiple visits for imaging sessions

Follow-up

Participants are monitored for safety and effectiveness after imaging procedures

4 weeks

Treatment Details

Interventions

• 18F-DPA-714
• 18F-FDG

Trial Overview The trial is testing a new PET imaging method using two tracers, 18F-FDG and 18F-DPA-714, to assess inflammation in both the liver and brain of patients with MASLD-related cognitive issues. This could help understand how liver disease might affect Alzheimer's Disease.

Participant Groups

Group I: Imaging Experimental Treatment 2 Interventions

Participants will undergo positron emission tomography scans. One scan will be performed after administration of 18F-FDG while the other will be perfomred after administration of 18F-DPA-714.

Who Is Running the Clinical Trial?

University of California, Davis

Lead Sponsor

Trials

958

Recruited

4,816,000+

Findings from Research

The study successfully simplified the synthesis of the PET radiopharmaceutical [(18)F]FEDAC, achieving high-quality clinical-grade batches with a decay-corrected radiochemical yield of up to 52%.

Acute toxicity tests in rats showed no harmful effects from a single dose of [(18)F]FEDAC over 14 days, indicating its safety for potential use in first-in-human studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficient radiosynthesis and non-clinical safety tests of the TSPO radioprobe [(18)F]FEDAC: Prerequisites for clinical application. Kawamura, K., Kumata, K., Takei, M., et al.[2018]

References

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

Hepatic glucose uptake is increased in association with elevated serum γ-glutamyl transpeptidase and triglyceride. [2021]

2. England pubmed.ncbi.nlm.nih.gov

FDG PET/CT of the non-malignant liver in an increasingly obese world population. [2021]

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

Effect of hepatic steatosis on liver FDG uptake measured in mean standard uptake values. [2016]

4. France pubmed.ncbi.nlm.nih.gov

[Management of non alcoholic fatty liver diseases in adults]. [2014]

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

Usefulness of controlled attenuation parameter in monitoring clinically relevant decline of hepatic steatosis for non-alcoholic fatty liver disease. [2023]

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

Efficient radiosynthesis and non-clinical safety tests of the TSPO radioprobe [(18)F]FEDAC: Prerequisites for clinical application. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Novel approach using [18F]FTHA-PET and de novo synthesized VLDL for assessment of FFA metabolism in a rat model of diet induced NAFLD. [2023]

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

Non-alcoholic fatty liver disease and type 2 diabetes mellitus: the liver disease of our age? [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Clinical translation of 18F-fluoropivalate - a PET tracer for imaging short-chain fatty acid metabolism: safety, biodistribution, and dosimetry in fed and fasted healthy volunteers. [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

Sensitive and early detection of mitochondrial dysfunction in the liver of NASH model mice by PET imaging with 18F-BCPP-BF. [2020]

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

Accumulation of (18)F-FDG in the liver in hepatic steatosis. [2016]

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

Pilot Study to Diagnose Nonalcoholic Steatohepatitis With Dynamic 18F-FDG PET. [2019]