Collagen-targeted PET Imaging for Early Interstitial Lung Disease

Study Overview
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Brief Summary
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The goal of this study is to investigate the ability of [68Ga]CBP8 to detect collagen deposition in early interstitial lung disease.

Detailed Description
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[68Ga]CBP8, is a PET imaging probe which selectively binds collagen type I. Collagen deposition is a pivotal event in the development of pulmonary fibrosis. [68Ga]CBP8 binds collagen with high affinity and has excellent pharmacological and pharmacokinetic profiles. [68Ga]CBP8 was shown in a mouse model to be effective for detecting lung fibrosis and response to treatment. In addition, [68Ga]CBP8 can detect increased collagen in the lungs of patients with idiopathic pulmonary fibrosis. The goals of this study are: To determine whether collagen deposition as assessed by [68Ga]CBP8-PET MRI can detect increased collagen deposition in early interstitial lung disease and if the degree of [68Ga]CBP8 uptake predicts subsequent disease progression.

Official Title
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Collagen-targeted PET Imaging for Early Interstitial Lung Disease

Conditions
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Interstitial Lung Disease

Intervention / Treatment
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* Drug: [68Ga]CBP8
* Drug: Dotarem


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Group 1: First degree relatives of a family member with pulmonary fibrosis (n=8) Age greater than 40 years Have the ability to give written informed consent First degree relative of a family member with pulmonary fibrosis No known history of interstitial lung disease No tobacco use within the prior 6 months. Group 2: Subjects with interstitial lung abnormalities (ILAs) or interstitial lung disease (ILD) (n=22) Age greater than 40 years Have the ability to give written informed consent ILAs or early ILD (defined by presence of reticular markings and / or traction bronchiectasis but absence of a definite UIP pattern) No tobacco use within the prior 6 months. Exclusion criteria: Electrical implants such as cardiac pacemaker or perfusion pump Ferromagnetic implants such as aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, metallic tattoos anywhere on the body, tattoos near the eye, or steel implants ferromagnetic objects such as jewelry or metal clips in clothing Historical eGFR of less than 30 mL/min/1.73 m2 Pregnant or breastfeeding (a negative quantitative serum hCG pregnancy test is required for females having child-bearing potential before the subject can participate) Claustrophobic reactions Research-related radiation exposure exceeds current Radiology Department guidelines (i.e. 50 mSv in the prior 12 months) Unable to lie comfortably on a bed inside the MR-PET BMI > 33 (limit of the PET-MRI table) Determined by the investigator(s) to be clinically unsuitable for the study (e.g. based on screening visit and/or during study procedures) Pneumonia or other acute respiratory illness within 6 weeks of study entry Parenchymal lung disease except for ILD/ILAs or emphysema Acute exacerbation of ILD within the prior 6 months VATS within the prior 6 months Prior radiation therapy to the thorax Known allergy to gadolinium.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Subjects with interstitial lung abnormalities (ILAs) or interstitial lung disease (ILD)<br>Subjects with interstitial lung abnormalities (ILAs) or interstitial lung disease (ILD) will receive [68Ga]CBP8 and undergo PET-MRI. | Drug: [68Ga]CBP8<br>* An injection of up to 350 MBq of [68Ga]CBP8 will be administered intravenously followed by PET-MRI.<br>Drug: Dotarem<br>* Dotarem will be administered during MRI portion of study.<br>* Other names: gadoterate meglumine;|
| Experimental: First degree relatives of a family member with pulmonary fibrosis<br>First degree relatives of a family member with pulmonary fibrosis will receive [68Ga]CBP8 and undergo PET-MRI. | Drug: [68Ga]CBP8<br>* An injection of up to 350 MBq of [68Ga]CBP8 will be administered intravenously followed by PET-MRI.<br>Drug: Dotarem<br>* Dotarem will be administered during MRI portion of study.<br>* Other names: gadoterate meglumine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Degree of uptake of [68Ga]CBP8 | The degree of uptake of [68Ga]CBP8 in the lungs will be compared between groups and associations with disease severity and progression will be determined. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of MRI contrast clearance, Kwashout, in the lungs | Kwashout rates will be compared between groups and associations with disease severity, progression, and degree of uptake of [68Ga]CBP8 will be determined. | 24 months | 
| Rate of MRI contrast arrival, Kwashin, in the lungs | Kwashin rates will be compared between groups and associations with disease severity, progression, and degree of uptake of [68Ga]CBP8 will be determined. | 24 months | 
| Peak enhancement of MRI contrast in the lungs | Peak enhancement will be compared between groups and associations with disease severity, progression, and degree of uptake of [68Ga]CBP8 will be determined. | 24 months |