PET Imaging CCR2 in Lung Inflammation

Study Overview
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Brief Summary
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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.

Detailed Description
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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). Healthy volunteers without known pulmonary disease will be recruited as controls (N=5). All subjects will be recruited and undergo one dynamic PET/CT scan to characterize the lung uptake of Cu-DOTA-ECL1i. Among those with pulmonary fibrosis imaging, an arterial catheter will be placed for blood draws in n=10 subjects, an additional sub group of subjects (n=10) will undergo a second PET/CT within two months. A third subgroup of subjects (n=10) who undergo lung transplant will have analysis of CCR2+ cells in their explanted lungs.

Official Title
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PET Imaging CCR2 in Lung Inflammation

Conditions
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Lung Inflammation

Intervention / Treatment
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* Drug: Cu-DOTA-ECL1i


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women 21 years of age or older who have never smoked or current smokers who smoked at least 10 cigarettes per day (1/2 pack) and have smoked at least 100 cigarettes (5 packs) over the past month. Screening FEV1 and FVC > 80% of predicted Capable of lying still and supine within the PET/CT and PET/MR scanner for  1 hour and follow instructions for breathing protocol during the CT portion No illicit drug use or other inhaled drug use (including pharmacologic agents, recreational agents, or illicit drugs) within the past year No known history of cardiac, pulmonary, hepatic or renal disease or diabetes No history of claustrophobia or other preventing condition that has previously or would interfere with completion of protocol specified imaging sessions Able to comprehend and willing to follow instructions for the study procedures as called for by the protocol BMI ≤ 35 Exclusion Criteria: Currently enrolled in another study using an investigational drug Pregnancy (confirmed by urine pregnancy test) Active symptoms or history of cardiac, pulmonary, hepatic or renal disease or diabetes Currently taking any prescription medications Presence of an implanted device that is incompatible with CT or MRI scanning Creatinine > 1.30 mg/dL, AST > 50 Units/L, ALT > 55 Units/L, or total bilirubin > 1.2 mg/dL

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 2 groups: Healthy Volunteers and Volunteers with Documented ILD Diagnosis
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy Volunteer Group<br>The healthy volunteer group will receive the same interventions as the ILD documented diagnosed volunteer group | Drug: Cu-DOTA-ECL1i<br>* Radiolabeled probe called Cu-DOTA-ECL1i that recognizes CCR2 and propose to image CCR2 in the lung to ultimately guide diagnosis and therapy.<br>|
| Experimental: ILD Documented Diagnosed Volunteer Group<br>The ILD documented diagnosed volunteer group will receive the same interventions as the healthy volunteer group | Drug: Cu-DOTA-ECL1i<br>* Radiolabeled probe called Cu-DOTA-ECL1i that recognizes CCR2 and propose to image CCR2 in the lung to ultimately guide diagnosis and therapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of uptake of Cu-DOTA-ECL1i to lung fibrosis | To establish the relation of lung uptake of Cu-DOTA-ECL1i compared to fibrosis determined by high resolution chest Computed tomography (CT) scan and clinical status | Through study completion | 
| Change of Cu-DOTA-ECL1i as measured by Positron emission tomography (PET) imaging of lung Standard uptake value (SUV) and Distribution Volume Ratio (DVR) over two months | Determine reproducibility of Cu-DOTA-ECL1i as measured by Positron emission tomography (PET) imaging of lung Standard uptake value (SUV) and Distribution Volume Ratio (DVR) over two months. | Through study completion | 
| Determine rate of kinetics of Cu-DOTA-ECL1i | Determine rate of kinetics of Cu-DOTA-ECL1i in circulation of blood at 0-60 min post-injection of Cu-DOTA-ECL1i by analysis of the arterial blood metabolites compared to lung uptake by Positron emission tomography/Computed tomography (PET/CT) imaging | Through study completion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine relationship between Cu-DOTA-ECL1i lung tissue as seen by Positron emission tomography (PET) imaging and lung tissue showing C-C Motif Chemokine Receptor 2 (CCR2+) cells | Determine relationship between Cu-DOTA-ECL1i lung tissue as seen by Positron emission tomography (PET) imaging and lung tissue showing C-C Motif Chemokine Receptor 2 (CCR2+) cells using pulmonary function measures | Through study completion |