Cu-DOTA-ECL1i Imaging for Lung Inflammation

Recruiting at 1 trial location

Overseen By Steven Brody, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Washington University School of Medicine

Must not be taking: Prescription medications

Disqualifiers: Cardiac, Pulmonary, Diabetes, 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

110 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the imaging agent Cu-DOTA-ECL1i can help doctors visualize lung inflammation in individuals with fibrotic lung diseases. The goal is to understand the agent's movement in the lungs and its ability to reliably indicate the presence of inflammatory cells. The study includes two groups: healthy volunteers and those with interstitial lung disease (ILD). Participants should be non-smokers or light smokers, free from major health issues like diabetes or heart disease, and comfortable with imaging tests. As an Early Phase 1 trial, this research aims to understand the imaging agent's function in people, offering participants the chance to contribute to this groundbreaking study.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any prescription medications to participate in this trial.

What prior data suggests that this imaging radiotracer is safe for humans?

Research shows that the radiotracer Cu-DOTA-ECL1i monitors inflammation in lung diseases. Studies with people have examined this compound's ability to detect specific inflammatory cells in the lungs. Although detailed safety information isn't available yet, earlier tests in human trials indicated some safety. As this is an early-phase study, the main goal is to understand how the body processes the treatment and to collect initial safety data. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Cu-DOTA-ECL1i because it offers a new way to visualize lung inflammation. Unlike typical treatments that manage symptoms or slow disease progression, Cu-DOTA-ECL1i is a diagnostic agent that targets specific inflammatory cells, providing a clearer picture of inflammation in the lungs. This innovative imaging approach could lead to earlier and more accurate diagnoses of lung conditions like interstitial lung disease (ILD), which might help tailor treatments more effectively to individual patients.

What evidence suggests that this imaging technique is effective for tracking lung inflammation?

Research has shown that Cu-DOTA-ECL1i effectively identifies lung inflammation by targeting specific cells responsible for it. In animal studies, this tracer appeared in areas with lung scarring. Early human trials also suggested that Cu-DOTA-ECL1i can successfully detect these inflamed areas. This trial will involve two groups: healthy volunteers and individuals with ILD (interstitial lung disease), both receiving Cu-DOTA-ECL1i to assess its effectiveness in detecting lung inflammation. This could make it a valuable tool for monitoring lung diseases involving inflammation. ^{1 2 3 4 6}

Who Is on the Research Team?

Steven Brody, MD

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for adults over 21 who either never smoked or are current smokers with a significant smoking history. They must be able to lie still for scans, have no illicit drug use in the past year, and normal lung function tests. Excluded are those with certain diseases, pregnant women, prescription medication users, and individuals with incompatible implanted devices.

Inclusion Criteria

You have not used illegal drugs or inhaled drugs (like prescription or recreational drugs) in the past year.

No history of claustrophobia or other preventing condition that has previously or would interfere with completion of protocol specified imaging sessions

I am 21 or older and either never smoked or currently smoke at least half a pack a day.

Exclusion Criteria

I am currently on prescription medication.

I have or had heart, lung, liver, kidney problems or diabetes.

You are pregnant, confirmed by a urine test.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants undergo a dynamic PET/CT scan to characterize the lung uptake of Cu-DOTA-ECL1i

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging

2 months

What Are the Treatments Tested in This Trial?

Interventions

• Cu-DOTA-ECL1i

Trial Overview

The study is testing Cu-DOTA-ECL1i as a PET imaging radiotracer to see how well it can show the distribution of inflammatory cells in patients' lungs with fibrotic diseases. It includes multiple sub-studies focusing on scan reproducibility and correlation between scan results and actual cell distribution.

How Is the Trial Designed?

Group I: ILD Documented Diagnosed Volunteer Group Experimental Treatment 1 Intervention

The ILD documented diagnosed volunteer group will receive the same interventions as the healthy volunteer group

Group II: Healthy Volunteer Group Experimental Treatment 1 Intervention

The healthy volunteer group will receive the same interventions as the ILD documented diagnosed volunteer group

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

The study developed a CCR2-binding peptide labeled with copper-64 for use as a PET radiotracer, which successfully detected lung inflammation in a mouse model, showing significantly higher PET signals in inflamed lungs compared to controls.

In human tissues, the radiotracer identified elevated CCR2 levels in lung tissue from COPD patients, indicating its potential for noninvasive detection of lung inflammation in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PET-based Imaging of Chemokine Receptor 2 in Experimental and Disease-related Lung Inflammation. Liu, Y., Gunsten, SP., Sultan, DH., et al.[2021]

VLA-4-targeted PET using the radiotracer 64Cu-LLP2A effectively detects inflammation in a mouse model of bleomycin-induced lung fibrosis, showing elevated uptake that correlates with disease progression and severity.

High uptake of 64Cu-LLP2A at an early stage (week 1) is a strong predictor of poor survival, indicating its potential as a prognostic tool for assessing the inflammation-fibrosis axis in lung diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted imaging of very late antigen-4 for noninvasive assessment of lung inflammation-fibrosis axis. Zhu, Q., Barnes, CE., Mannes, PZ., et al.[2023]

The study successfully used 64Cu-DOTA-ECL1i PET imaging to detect proinflammatory CCR2+ monocytes and macrophages in various heart injury models, demonstrating its effectiveness and specificity.

Flow cytometry confirmed that CCR2 is specifically expressed on these immune cells, and the tracer also binds to human CCR2, paving the way for potential clinical applications in imaging heart diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted PET Imaging of Chemokine Receptor 2-Positive Monocytes and Macrophages in the Injured Heart. Heo, GS., Bajpai, G., Li, W., et al.[2022]

The study demonstrated that the copper transporter 1 (CTR1) is overexpressed in various lung cancer cell lines, and the uptake of the tracer copper (II)-64 chloride (64CuCl2) is directly related to the levels of CTR1 expression, indicating its potential for targeted imaging.

Small animal PET imaging confirmed that 64CuCl2 can effectively visualize CTR1 expression in lung cancer tumors, suggesting it could be a valuable tool for PET imaging in clinical lung cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical PET imaging study of lung cancer with 64CuCl2. Wang, Q., Song, D., Ma, X., et al.[2022]

The study developed a radiotracer, 64Cu-DOTA-ECL1i, to noninvasively track CCR2+ monocytes and macrophages in patients with idiopathic pulmonary fibrosis (IPF), showing that increased uptake of this tracer correlates with CCR2+ cell infiltration in fibrotic lung regions.

Inhibition of fibrosis through treatments like IL-1β blockade or antifibrotic pirfenidone reduced CCR2+ macrophage accumulation, indicating that targeting these cells could be a promising approach for personalized therapy in IPF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemokine Receptor 2-targeted Molecular Imaging in Pulmonary Fibrosis. A Clinical Trial. Brody, SL., Gunsten, SP., Luehmann, HP., et al.[2022]

The study demonstrated that 64CuCl₂ can effectively target and image inflammation in animal models, showing significantly higher accumulation in inflamed tissues compared to controls, indicating its potential as a PET imaging agent.

Increased expression of the copper transporter CTR1 in inflammatory tissues was confirmed through immunohistochemical staining and western blot analysis, supporting the mechanism by which 64CuCl₂ accumulates in these areas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot Study of 64CuCl&#8322; for PET Imaging of Inflammation. Jiang, L., Song, D., Chen, H., et al.[2019]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03492762

NCT03492762 | PET Imaging CCR2 in Lung Inflammation

This is a single site, pilot Phase 0/1 clinical trial to establish the uptake of Cu-DOTA-ECL1i in additional patients with ILD fibrotic lung disease (n=60).

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7781144/

Chemokine Receptor 2–targeted Molecular Imaging in ...

We hypothesize that 64Cu-DOTA-ECL1i detects the CCR2+ cell inflammatory process associated with pulmonary fibrosis and can be used to monitor disease activity.

3.

withpower.com

withpower.com/trial/early-phase-1-pneumonia-1-2018-60de0

Cu-DOTA-ECL1i Imaging for Lung Inflammation

Research shows that 64Cu-DOTA-ECL1i can effectively detect lung inflammation by targeting specific cells involved in the inflammatory process. In studies with ...

4.

sciencedirect.com

sciencedirect.com/science/article/pii/S1568997222001720

Novel tracers for molecular imaging of interstitial lung ...

The CCR2 specific tracer 64Cu-DOTA-ECL1i was investigated in one study with ex-vivo human lung tissue, the BLM mouse model and in human subjects with IPF. 64Cu- ...

5.

jnm.snmjournals.org

jnm.snmjournals.org/content/62/supplement_1/1695

Chemokine receptor 2 targeted PET imaging in pulmonary ...

Results: In the bleomycin mouse model, 64Cu-DOTA-ECL1i PET showed intensive lung uptake associated with perifibrotic regions which peaked at day ...

6.

biorxiv.org

biorxiv.org/content/10.1101/2020.03.04.960179v1.full.pdf

Chemokine receptor 2-targeted molecular imaging in ...

As an alternative, we examined 64Cu-DOTA-ECL1i PET lung activity in a mouse model of radiation-induced injury and fibrosis. Radiation injury is ...