[18F]NOS PET/CT Scan for Neuroinflammation

Recruiting in Palo Alto (17 mi)

Overseen by Jacob Dubroff, MD, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: University of Pennsylvania

Must be taking: ART, OUD treatment

Disqualifiers: Pregnancy, Epilepsy, Schizophrenia, Claustrophobia, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The purpose of this research is to measure the extent of inflammation in the brain between different groups of participants using a radioactive tracer called \[18F\]NOS. A radioactive tracer is a type of imaging drug that is labeled with a radioactive tag and injected into the body. This study will see how the tracer is taken up in the brain using an imaging scan called Positron Emission Tomography / Computed Tomography (PET/CT). Participants will undergo approximately 60 minutes of dynamic scanning of the brain starting at approximately the time of injection of \[18F\]NOS. Participants are required to have a brain MRI performed within 1 year prior to study enrollment, or if the subject has not had a brain MRI that is deemed acceptable for use for this study they will be asked to undergo a research brain MRI after they have consented for this study.

Will I have to stop taking my current medications?

The trial requires participants with HIV to stay on a stable ART regimen (HIV treatment) and those with OUD to be on a stable dosage of OUD treatment for at least four weeks before the screening. The protocol does not specify other medication restrictions.

How does the [18F]NOS PET/CT scan differ from other treatments for neuroinflammation?

The [18F]NOS PET/CT scan is unique because it uses a radiolabeled tracer to specifically target and visualize inducible nitric oxide synthase (iNOS), a key enzyme involved in neuroinflammation, allowing for non-invasive imaging of inflammation in the brain. This approach is different from traditional treatments as it focuses on detecting and measuring inflammation rather than directly treating it. ^{1 2 3 4 5}

Research Team

Jacob Dubroff, MD, PhD

Principal Investigator

University of Pennsylvania

Eligibility Criteria

This trial is for adults aged 18-65 with or without HIV and opioid use disorder (OUD). Participants must have stable health conditions, including a controlled viral load if HIV positive, and be on consistent OUD treatment if applicable. Pregnant or breastfeeding women, individuals over 350 lb, those with claustrophobia affecting scans, MRI contraindications like incompatible metal in the body, significant organ dysfunction, epilepsy/seizure disorders, severe head trauma history, certain psychiatric disorders including schizophrenia or active major depression with suicidal ideation are excluded.

Inclusion Criteria

I am 18-65, HIV negative, have never had opioid use disorder, and haven't used opioids in the last 30 days.

I am 18-65, have HIV and opioid use disorder, on stable treatments for both, and my viral load and CD4+ count are within required ranges.

I am 18-65, HIV positive, not using opioids, with controlled HIV on stable treatment.

Exclusion Criteria

Claustrophobia that may interfere with MRI acquisition or PET scan

Current psychiatric disorder

History of head trauma

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants undergo PET/CT imaging to measure neuroinflammation using [18F]NOS tracer

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging

4 weeks

Treatment Details

Interventions

• [18F]NOS (Radioactive Tracer)
• FNOS (Radioactive Tracer)

Trial Overview The study tests how a radioactive tracer called [18F]NOS behaves in the brain to measure inflammation levels using PET/CT imaging. It involves an injection of [18F]NOS followed by about an hour-long dynamic brain scan. The research includes people both with and without HIV/OUD to compare results across different health statuses.

Participant Groups

Group I: Healthy volunteer Experimental Treatment 1 Intervention

HIV-, OUD- healthy controls who have been opioid-exposed but do not have current or past OUD

Group II: HIV positive (HIV+) subjects with Opioid Use Disorder (OUD) Experimental Treatment 1 Intervention

HIV positive (HIV+) subjects with Opioid Use Disorder (OUD): HIV+/OUD+

Group III: HIV negative (HIV-) subjects with OUD Experimental Treatment 1 Intervention

HIV negative (HIV-) subjects with OUD: HIV-/OUD+

Group IV: HIV Positive (HIV+) subjects with OUD negative Experimental Treatment 1 Intervention

HIV+ subjects who may have been opioid-exposed but do not have current or past OUD

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Dr. Joan Lau

University of Pennsylvania

Chief Executive Officer since 2020

PhD in Neuroscience from the University of Cincinnati College of Medicine, MBA from the Wharton School of Business, BS in Bioengineering from the University of Pennsylvania

Dr. Robert Iannone

University of Pennsylvania

Chief Medical Officer since 2019

MD from Yale University, MSCE from the University of Pennsylvania

Findings from Research

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]

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]

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 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]

References

1. England 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. [2021]

2. United States 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. [2021]

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

Synthesis of a Potent Aminopyridine-Based nNOS-Inhibitor by Two Recent No-Carrier-Added (18)F-Labelling Methods. [2020]

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

Feasibility and dosimetry studies for 18F-NOS as a potential PET radiopharmaceutical for inducible nitric oxide synthase in humans. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

[18F]NOS PET Brain Imaging Suggests Elevated Neuroinflammation in Idiopathic Parkinson's Disease. [2023]