18F-NOS PET/CT Scan for Parkinson's Disease

Overseen By Erin Schubert

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Pennsylvania

Must not be taking: CNS drugs

Disqualifiers: Pregnancy, Epilepsy, Head trauma, Nicotine, Alcohol, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to determine if a special PET/CT scan using the imaging drug 18F-NOS can help diagnose or monitor Parkinson's disease by measuring brain inflammation. The trial includes two groups: individuals with Parkinson's for at least three years and healthy individuals. Those with Parkinson's may qualify if they have been diagnosed for at least three years and can safely participate according to a neurologist. As an Early Phase 1 trial, this research focuses on understanding how the imaging drug works in people, offering participants a chance to contribute to groundbreaking diagnostic advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are in the healthy control group, you cannot use any central nervous system (CNS) drugs within 30 days of screening.

What prior data suggests that this PET/CT scan is safe for humans?

Previous studies have tested the 18F-NOS PET/CT scan in people, including heart transplant recipients. This research focused on assessing the scan's safety and effectiveness for imaging. So far, studies have not revealed any major safety concerns. As the 18F-NOS is now used in an early phase trial for Parkinson's disease, researchers continue to gather safety information. However, its prior testing in other contexts suggests it is generally well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the 18F-NOS PET/CT scan for Parkinson's disease because it offers a new way to visualize and understand brain inflammation, which is a key aspect of the disease. Unlike existing treatments that mainly focus on managing symptoms like tremors and stiffness, this technique uses the radiotracer [18F]NOS to provide detailed images of nitric oxide synthase activity in the brain. This could allow for earlier and more precise detection of Parkinson's disease progression, potentially leading to better-targeted therapies in the future.

What evidence suggests that this PET/CT scan is effective for diagnosing or monitoring Parkinson's disease?

Research has shown that the [18F]NOS PET/CT scan can detect brain inflammation by measuring oxidative stress, often elevated in early-stage Parkinson's disease. This trial will include participants with Parkinson's disease and healthy controls to assess the scan's effectiveness. Researchers have tested the scan on individuals with various conditions to confirm its safety and efficacy for imaging. Early results suggest that [18F]NOS could aid in understanding and tracking Parkinson's disease by highlighting inflammation areas. The goal is to offer a clearer view of brain changes in Parkinson's, potentially improving disease management. ^{1 2 6 7 8}

Who Is on the Research Team?

Jacob Dubroff, MD, PhD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

This trial is for people aged 18-75 with Parkinson's disease or healthy individuals interested in brain inflammation research. Participants must understand the study and agree to its procedures. Those with neuropsychiatric disorders can join if it doesn't risk their safety or participation, as judged by an investigator.

Inclusion Criteria

History of diagnosis of probable idiopathic PD derived from UK Brain Bank Diagnostic criteria(1) per neurologist review.

I was diagnosed with Parkinson's Disease over 3 years ago.

Subjects with known neuropsychiatric disorder may be eligible if, in the opinion of an investigator, the psychiatric condition would not compromise subject safety or successful participation in the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants undergo one experimental 18F-NOS PET/CT scan to measure brain inflammation

1 day

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]NOS

Trial Overview The study tests a PET/CT scan using a tracer called 18F-NOS to detect brain inflammation, which could help diagnose or monitor Parkinson's disease treatment effectiveness.

How Is the Trial Designed?

Group I: Patient with Parkinson Disease Experimental Treatment 1 Intervention

Subject should have a history of diagnosis of probable idiopathic PD derived from UK Brain Bank Diagnostic criteria per neurologist review. Subject must have been diagnosed with Parkinson's Disease at least 3 year prior to enrollment.

Group II: Healthy Control Experimental Treatment 1 Intervention

Subject must be a Healthy.

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Published Research Related to This Trial

The study demonstrated that myocardial (18)F-NOS activity is significantly higher in heart transplant patients experiencing organ rejection, indicating its potential as a marker for assessing iNOS activity related to inflammation.

The (18)F-NOS radiopharmaceutical showed acceptable radiation exposure levels, with the bladder wall being the critical organ, suggesting it could be safely used in humans for monitoring iNOS levels in various diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility and dosimetry studies for 18F-NOS as a potential PET radiopharmaceutical for inducible nitric oxide synthase in humans. Herrero, P., Laforest, R., Shoghi, K., et al.[2021]

In a pilot study involving 10 adults (6 with Parkinson's disease and 4 healthy controls), researchers found that neuroinflammation, indicated by increased levels of the [18F]NOS radiotracer, was significantly higher in Parkinson's patients compared to healthy individuals.

The study suggests that [18F]NOS PET imaging could be a valuable non-invasive tool for measuring neuroinflammation in early-stage Parkinson's disease, highlighting the role of oxidative stress in the disease's pathology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[18F]NOS PET Brain Imaging Suggests Elevated Neuroinflammation in Idiopathic Parkinson's Disease. Doot, RK., Young, AJ., Nasrallah, IM., et al.[2023]

A highly selective nNOS inhibitor was successfully labeled with the radioactive isotope (18)F, achieving a radiochemical yield of 79%, which allows for its use in molecular imaging to study nitric oxide synthase function in neurodegenerative disorders.

Two effective methods for labeling the nNOS inhibitor were developed, providing options for preclinical studies to investigate the role of nitric oxide in neurodegeneration, with a total radiochemical yield of about 15% for the final product.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis of a Potent Aminopyridine-Based nNOS-Inhibitor by Two Recent No-Carrier-Added (18)F-Labelling Methods. Drerup, C., Ermert, J., Coenen, HH.[2020]

The study successfully developed a new PET imaging tracer, [18F]FBAT, which can detect inducible nitric oxide synthase (iNOS) activity in a mouse model of neuroinflammation, indicating its potential as a biomarker for neuroinflammation.

In vivo imaging showed that [18F]FBAT accumulation was significantly higher in LPS-treated mice compared to controls, and this accumulation was reduced by an iNOS inhibitor, confirming the tracer's specificity for iNOS in neuroinflammatory conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Automated Synthesis and Initial Evaluation of (4'-Amino-5',8'-difluoro-1'H-spiro[piperidine-4,2'-quinazolin]-1-yl)(4-[18F]fluorophenyl)methanone for PET/MR Imaging of Inducible Nitric Oxide Synthase. Yeh, SH., Huang, WS., Chiu, CH., et al.[2021]

Positron emission tomography (PET) has been instrumental in visualizing dopaminergic structures in the human brain, revealing that presynaptic dopamine insufficiency can be detected in Parkinson's disease (PD) using 18F-fluorodopa, while striatal dopaminergic terminals remain relatively preserved compared to post-mortem findings.

PET studies using 11C-nomifensine and 11C-selegiline have shown that dopamine reuptake sites are visualized and that therapeutic doses of MAO-B inhibitors can effectively inhibit enzyme activity, providing insights into the mechanisms of treatment in both early and advanced stages of PD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What has PET told us about Parkinson's disease? Aquilonius, SM.[2019]

The compound [(18)F]9 was identified as a promising PET tracer for imaging inducible nitric oxide synthase (iNOS), showing higher uptake in the lungs of mice with LPS-induced iNOS activation compared to control mice.

In vivo studies confirmed the specificity of [(18)F]9 for iNOS, as tracer uptake was significantly reduced when a known iNOS inhibitor was used, indicating its potential for accurate imaging of iNOS activation in inflammatory conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design and synthesis of 2-amino-4-methylpyridine analogues as inhibitors for inducible nitric oxide synthase and in vivo evaluation of [18F]6-(2-fluoropropyl)-4-methyl-pyridin-2-amine as a potential PET tracer for inducible nitric oxide synthase. Zhou, D., Lee, H., Rothfuss, JM., et al.[2021]

Current molecular PET imaging techniques for neurodegenerative parkinsonism focus on radiotracers that visualize vulnerable neuron terminals, but they do not effectively differentiate between various parkinsonian conditions based on neurotransmitter loss.

Research is ongoing to develop new imaging ligands using advanced molecular modeling to better target specific proteinopathies associated with these disorders, although current PET imaging methods face challenges such as the need for automated analysis and limited insurance coverage in the U.S.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular Imaging of Neurodegenerative Parkinsonism. Frey, KA., Bohnen, NILJ.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9563966/

[18F]NOS PET Brain Imaging Suggests Elevated ... These findings suggest elevated oxidative stress, a surrogate marker of inflammation, is present in early-stage idiopathic PD.

2. withpower.com withpower.com/trial/early-phase-1-parkinson-disease-7-2019-9312a

18F-NOS PET/CT Scan for Parkinson's Disease The 18F-NOS PET/CT scan has been evaluated in humans, including patients after heart transplantation, to measure its safety and effectiveness in imaging ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04062526

Evaluation of Neuroinflammation in Parkinson's Disease ... [18F]NOS is an investigational radiotracer which each subject will have one [18F]NOS positron emission tomography/computed tomography (PET/CT) scan performed.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11429636/

Brain Evaluation by Dual PET/CT with [18F] FDOPA and ... Conclusions: Dual FDOPA–FDG PET/CT demonstrated moderate agreement with the initial clinical diagnosis of Parkinsonism and moderate to ...

5. imaging-cro.biospective.com imaging-cro.biospective.com/resources/fdopa-parkinsons-disease-clinical-trials

[18F]DOPA PET in Parkinson's Disease Clinical Trials [18F]DOPA PET is used to monitor disease progression & response to therapeutic intervention in Parkinson's disease & movement disorders clinical trials.

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK23142/

[18F]6-(2-Fluoropropyl)-4-methyl-pyridin-2-amine - NCBI - NIH Nitric oxide (NO) is produced as an important mediator in physiological and pathophysiological conditions by three isoforms of NO synthase (NOS): ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2019/200655Orig1s000MultidisciplineR.pdf

Multi-Discipline Review - accessdata.fda.gov Used in Positron Emission Tomography (PET) to visualize dopaminergic in the striatum adult patients with suspected Parkinsonian syndromes (PS).

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2782628/

4-methyl-pyridin-2-amine as a Potential PET Tracer for ... In conclusion, [18F]6-(2-Fluoropropyl)-4-methylpyridin-2-amine ([18F]9) is a potential radiotracer for PET imaging of iNOS expression. Experimental Section.