Cu-DOTA-ECL1i Imaging for Lung Inflammation

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?

The primary objective of this study is to assess the lung distribution of the Positron Emission Tomography (PET) imaging radiotracer Cu-DOTA-ECL1i, which binds to the specific population inflammatory cells, in patients with fibrotic lung diseases. This objective includes sub-studies to assess radiotracer distribution in the lung, the reproducibility of PET scans and the relationship of the scan to distribution of inflammatory cells in human lung tissue. The overall goal is to assess the potential of the radiotracer to track inflammatory cells in lung diseases.

Will I have to stop taking my current medications?

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

How does Cu-DOTA-ECL1i differ from other treatments for lung inflammation?

Cu-DOTA-ECL1i is unique because it uses a PET imaging technique to noninvasively detect lung inflammation by targeting CCR2, a specific receptor on immune cells involved in inflammation. This approach allows for precise visualization of inflammation, which is different from traditional treatments that may not provide such targeted imaging capabilities. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment Cu-DOTA-ECL1i, 64Cu-DOTA-ECL1i 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 mice and human tissues, this treatment successfully identified areas of lung inflammation, suggesting it could be a useful tool for diagnosing and monitoring lung conditions. ^{1 3 4 5 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

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

I can lie still for an hour and follow breathing instructions during a scan.

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

Exclusion Criteria

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

I am currently on prescription medication.

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]

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 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 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]

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]

Citations

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

PET-based Imaging of Chemokine Receptor 2 in Experimental and Disease-related Lung Inflammation. [2021]

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

Chemokine Receptor 2-targeted Molecular Imaging in Pulmonary Fibrosis. A Clinical Trial. [2022]

3. Japan pubmed.ncbi.nlm.nih.gov

Preclinical PET imaging study of lung cancer with 64CuCl2. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Pilot Study of 64CuCl&#8322; for PET Imaging of Inflammation. [2019]

5. Germany pubmed.ncbi.nlm.nih.gov

Targeted imaging of very late antigen-4 for noninvasive assessment of lung inflammation-fibrosis axis. [2023]

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

Targeted PET Imaging of Chemokine Receptor 2-Positive Monocytes and Macrophages in the Injured Heart. [2022]