[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

Trial Summary

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 data supports the effectiveness of the drug [18F]NOS 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. This suggests it could be a useful tool for imaging and monitoring lung inflammation. ^{1 2 3 4 5}

Is [18F]NOS safe for use in humans?

Research indicates that [18F]NOS has been evaluated in humans for imaging purposes, particularly in the context of lung inflammation and heart transplant patients. While specific safety data is not detailed, its use in human studies suggests a level of safety that supports further investigation. ^{1 2 3 4 5}

How does the drug [18F]NOS differ from other treatments for lung inflammation?

[18F]NOS is unique because it is a PET imaging tracer specifically designed to bind to inducible nitric oxide synthase (iNOS), which is a marker of inflammation in the lungs. Unlike traditional treatments that aim to reduce inflammation, this drug helps visualize and quantify inflammation, providing a novel way to monitor lung disease activity. ^{1 2 3 4 5}

What is the purpose of this trial?

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. A radioactive tracer is a type of imaging drug that is labeled with a radioactive tag and injected into the body.

Research Team

Jacob Dubroff, MD, PhD

Principal Investigator

University of Pennsylvania

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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: 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 III: 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 IV: 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 V: 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+

Findings from Research

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 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]

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]

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 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]

References

1. 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]

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. 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]

4. United States 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. [2018]

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

Imaging pulmonary inducible nitric oxide synthase expression with PET. [2018]