[18F]NOS PET/CT Scan for Neuroinflammation

Overseen By Erin Schubert

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Pennsylvania

Must be taking: ART, OUD treatment

Disqualifiers: Pregnancy, Epilepsy, Schizophrenia, Claustrophobia, others

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

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to measure brain inflammation using a special imaging scan with a radioactive tracer called [18F]NOS, which allows researchers to observe inflammation differences among various groups. It includes individuals with HIV, those with Opioid Use Disorder (OUD), and healthy volunteers. Each group will undergo a brain scan to observe tracer absorption. Participants should have either HIV, a history of OUD, or be healthy volunteers who have been exposed to opioids in the past but do not have OUD. As an Early Phase 1 trial, this research focuses on understanding how the tracer functions in people, offering participants a chance to contribute to groundbreaking scientific discovery.

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.

What prior data suggests that this imaging technique is safe for measuring neuroinflammation?

Research shows that [18F]NOS, a special substance used in PET/CT scans, is still under testing, so complete safety information is not yet available. In similar studies, these substances have helped doctors detect brain inflammation. Tests with other similar substances suggest they are usually safe, but each one can differ.

Since this study is in the early stages, it primarily examines the safety and effectiveness of the substance. Early studies typically involve a small group of people, allowing researchers to closely monitor any side effects. So far, similar substances in other studies have not reported major problems. However, because [18F]NOS is new, participants should discuss any concerns with the study team.

In summary, while specific safety data for [18F]NOS is not yet available, similar substances in other studies have been used without major issues. This study provides an opportunity to learn more about its safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the [18F]NOS PET/CT scan because it offers a new way to visualize neuroinflammation in the brain, which is not something standard treatments for conditions like HIV and opioid use disorder (OUD) typically address. This approach uses a special tracer, [18F]NOS, which binds to areas of inflammation, allowing doctors to see the extent of neuroinflammation via advanced imaging. Unlike traditional methods that might rely on indirect assessments or symptoms, this PET/CT technique provides a direct and clear picture of brain inflammation. By doing so, it could help tailor treatments more precisely and improve understanding of how conditions like HIV and OUD affect brain health.

What evidence suggests that this imaging method is effective for measuring neuroinflammation?

Research has shown that the [18F]NOS tracer holds promise for detecting brain inflammation, which results from immune activity. Studies have demonstrated that it can visualize inflammation by highlighting areas where the enzyme iNOS is active. This enzyme often appears in large amounts during inflammation, making the tracer a valuable imaging tool. In earlier human studies, [18F]NOS successfully identified inflammation in heart tissue. Although research continues, these initial findings suggest that [18F]NOS could also effectively detect brain inflammation. Participants in this trial will undergo [18F]NOS PET/CT scans to evaluate its effectiveness in detecting neuroinflammation across different groups, including those with HIV and/or Opioid Use Disorder (OUD), as well as healthy volunteers. ^{1 6 7 8 9}

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 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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• [18F]NOS
• FNOS

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

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

[18F]6-(2-Fluoropropyl)-4-methyl-pyridin-2-amine - NCBI - NIH In contrast, activated iNOS can generate a large amount of NO over a prolonged period of time during acute and chronic inflammatory diseases (3) ...

2. researchgate.net researchgate.net/publication/24236361_Design_and_Synthesis_of_2-Amino-4-methylpyridine_Analogues_as_Inhibitors_for_Inducible_Nitric_Oxide_Synthase_and_in_Vivo_Evaluation_of_18F6-2-Fluoropropyl-4-methyl-pyridin-2-amine_as_a_Potential_PET_T

4-methyl-pyridin-2-amine as a Potential PET Tracer for ... In its first human application, elevated [ 18 F]6-(1/2)(2-fluoropropyl)-4-methylpyridin-2-amine ([ 18 F]NOS) myocardial uptake predicted cardiac ...

3. reporter.nih.gov reporter.nih.gov/search/5kMjkxk4gEuNMLyi6cpjpw/project-details/11121918

RePORT ⟩ RePORTER We're sorry but RePORTER doesn't work properly without JavaScript enabled. Please enable it to continue.

4. researchgate.net researchgate.net/publication/370006679_Positron_emission_tomography_imaging_of_neuroinflammation

Positron emission tomography imaging of neuroinflammation ... ([¹⁸F]FFDI), which is based on FFDI, has been reported to act as a PET radiotracer for iNOS [15]. Moreover, [¹⁸F]6-(2-fluoropropyl)-4-methyl-pyridin-2-amine ([ ...

5. medrxiv.org medrxiv.org/content/10.1101/2022.06.15.22276438v1.full-text

Using 18 F-NOS PET Imaging to Measure Pulmonary ... We found preliminary evidence EC users had greater pulmonary inflammation than cigarette smokers and never smoke/vape controls.

6. 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.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04401917

Evaluation of Neuroinflammation FNOS PET/CT in HIV ... The purpose of this research is to measure the extent of inflammation in the brain between different groups of participants using a radioactive tracer ...

8. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK23142/table/iNOS-9-18F.T1/

Molecular Imaging and Contrast Agent Database (MICAD ... 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 ...

9. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-04886

Fluorine F 18 Nitric Oxide Synthase PET/CT for the ... This phase I trial evaluates the extent of brain and other organ inflammation using a radioactive tracer called fluorine F 18 (18F) nitric oxide synthase ...