[18F]NOS Imaging for Lung Inflammation

Overseen By Erin Schubert

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Pennsylvania

Must not be taking: Corticosteroids, Anti-inflammatories

Disqualifiers: Pregnancy, Substance use disorder, 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

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to study how a radioactive tracer, called [18F]NOS, measures lung inflammation in various smokers and non-smokers. The goal is to compare the effects of smoking habits, such as traditional cigarette smoking or vaping, on lung health with those of non-smokers. Participants may include individuals who smoke cigarettes, use e-cigarettes for nicotine or cannabis, or have a history of minimal smoking and vaping. Those who regularly smoke or vape, or have avoided smoking, may find this trial suitable. As a Phase 1 trial, this research focuses on understanding how the tracer functions in people, offering participants the chance to contribute to this groundbreaking study.

Will I have to stop taking my current medications?

The trial requires that participants do not use inhaled or oral corticosteroids or anti-inflammatory medications. If you are taking these, you may need to stop before joining the study.

What prior data suggests that the [18F]NOS imaging technique is safe for measuring lung inflammation?

Research has shown that [18F]NOS has been used in human studies, suggesting it is safe enough for further research. Although detailed safety information is not yet available, its testing in people is promising. This radioactive tracer helps doctors visualize lung inflammation in various groups. As it is in the early trial phase, researchers continue to learn about its safety, closely monitoring for any side effects or issues. Prospective trial participants should know that early studies like this prioritize ensuring the treatment's safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the [18F]NOS Imaging for Lung Inflammation trial because it offers a novel way to visualize lung inflammation, setting it apart from existing methods. Unlike traditional imaging techniques, [18F]NOS targets specific enzymes linked to inflammation, potentially allowing for more precise and earlier detection of lung issues. This innovative approach could significantly enhance our understanding of how smoking and vaping affect lung health, providing insights that could lead to better treatment strategies in the future.

What evidence suggests that [18F]NOS is effective for measuring lung inflammation?

Research has shown that a substance called [18F]NOS can attach to a protein linked to inflammation, aiding in measuring inflammation levels in the lungs. This trial will use [18F]NOS to image lung inflammation in various groups, including traditional cigarette smokers, nicotine vapers, cannabis vapers, dual smokers/vapers, poly-use nicotine and cannabis users, and non-smokers. Previous studies have successfully used [18F]NOS to image lung inflammation in animals with lung injuries. Additionally, research found that e-cigarette users had higher [18F]NOS levels than both traditional smokers and non-smokers. These findings suggest that [18F]NOS might effectively detect lung inflammation. ^{1 2 3 4 6}

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 18-45 who are non-smokers, regular e-cigarette users (nicotine or cannabis), cigarette smokers, or dual users of cigarettes and e-cigarettes. Participants must not have lung diseases like tuberculosis, be on steroids/anti-inflammatory drugs, have untreated major depression/psychosis, or a history of lung trauma. Pregnant/breastfeeding women and those with certain drug use are excluded.

Inclusion Criteria

I smoke at least 5 cigarettes daily and haven't used e-cigarettes in the last 30 days.

I've been using e-cigarettes for cannabis almost daily for the past year and haven't smoked cigarettes, cannabis, or used nicotine vapes in the last month.

I've used e-cigarettes and smoked cigarettes or cannabis almost daily for the last year.

Exclusion Criteria

You are currently not receiving treatment for a substance use disorder, except for nicotine or cannabis use disorder.

I haven't had a lung infection or disease affecting [18F]NOS uptake in the last 4 weeks.

Inability to tolerate imaging procedures in the opinion of an investigator or treating physician

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 lung and 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 [18F]NOS, a radioactive tracer used in imaging to measure lung inflammation caused by smoking/vaping habits among different groups. The study involves injecting this substance into the body to track inflammation levels using special imaging techniques.

How Is the Trial Designed?

Group I: Traditional Cigarette Smokers Experimental Treatment 1 Intervention

Reported current cigarette smoking of at least 5 cigarettes per day, 5 days per week for the past 1 year with no history of e-cigarette use (cannabis or nicotine) during the 30 days prior to study enrollment

Group II: Poly-use nicotine and cannabis group Experimental Treatment 1 Intervention

Poly-use nicotine and cannabis group: current e-cigarette use of nicotine and/or cigarette use (5 cigarettes per day) and/or use of cannabis, at least 4 days per week during the 30 days prior to study enrollment.

Group III: Non-Smokers Experimental Treatment 1 Intervention

Reported non-smoking history or \< 100 lifetime cigarettes, \< 100 e-cigarette use episodes and \< 100 lifetime cannabis use episodes

Group IV: Nicotine Vapers Experimental Treatment 1 Intervention

Reported current e-cigarette use of nicotine at least 5 days per week for the past year with no current combustible cigarette use, cannabis vaping or cannabis smoking during the 30 days prior to study enrollment

Group V: Dual Smokers/Vapers Experimental Treatment 1 Intervention

Reported current e-cigarette use of cannabis and/or nicotine at least 5 days per week for the past year with cigarette or cannabis smoking during the 30 days prior to study enrollment

Group VI: Cannabis Vapers Experimental Treatment 1 Intervention

Reported current e-cigarette use of cannabis at least 5 days per week for the past year, no current combustible cigarette use, cannabis smoking or nicotine vaping during the 30 days prior to study enrollment

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 novel PET tracer (18)F-NOS successfully quantified iNOS expression in healthy volunteers after inducing lung inflammation with endotoxin, showing a significant increase in iNOS activity (30% increase in distribution volume ratio).

This study suggests that (18)F-NOS could serve as a valuable imaging tool for monitoring inflammation in lung diseases, as it effectively detects changes in iNOS expression associated with acute lung inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imaging pulmonary inducible nitric oxide synthase expression with PET. Huang, HJ., Isakow, W., Byers, DE., et al.[2018]

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 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]

Two new positron-emitting inhibitors for inducible nitric oxide synthase (iNOS) were developed, showing a 9-fold higher selectivity for iNOS over endothelial NOS, which is crucial for accurately probing iNOS levels in vivo.

In vivo studies in LPS-pretreated rats demonstrated that both tracers effectively increased uptake in tissues known to express iNOS, indicating their potential utility for assessing iNOS induction using positron emission tomography (PET).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and evaluation of two positron-labeled nitric oxide synthase inhibitors, S-[11C]methylisothiourea and S-(2-[18F]fluoroethyl)isothiourea, as potential positron emission tomography tracers. Zhang, J., McCarthy, TJ., Moore, WM., et al.[2018]

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]

Citations

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

[18F]6-(2-Fluoropropyl)-4-methyl-pyridin-2-amine - NCBI - NIH One of them, [18F]6-(2-fluoropropyl)-4-methyl-pyridin-2-amine ([18F]iNOS-9), has been tested in mice. Go to: Synthesis. [PubMed]. [18F]iNOS-9 ...

2. jnm.snmjournals.org jnm.snmjournals.org/content/64/5/797

Molecular Imaging of Pulmonary Inflammation in Users of ... F-NOS has been validated in an animal model of lipopolysaccharide-induced lung injury (29) and was used successfully to image iNOS expression in ...

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

Using 18 F-NOS PET Imaging to Measure Pulmonary ... These findings strongly support iNOS as a mechanistically relevant target for molecular imaging of lung inflammation and inflammatory lung ...

4. withpower.com withpower.com/trial/phase-1-pneumonia-9-2018-e18c9

[18F]NOS Imaging for Lung Inflammation Research shows that [18F]NOS can successfully bind to inducible nitric oxide synthase (iNOS), which is linked to inflammation, in both human and animal studies.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36657981/

Molecular Imaging of Pulmonary Inflammation in Users of ... Results: EC users showed greater 18F-NOS nondisplaceable binding potential (BPND) than cigarette smokers (P = 0.03) and controls (P = 0.01), whereas BPND in ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03721822

Imaging Sex Differences in Smoking-Induced Pulmonary ... The purpose of this research is to measure the extent of lung inflammation between different groups of participants using a radioactive tracer called [18F]NOS.