Advanced Imaging for Pulmonary Fibrosis

The purpose of this study is to determine if measurements of active collagen deposition using [68Ga]CBP8 positron emission tomography (PET) and tissue injury using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can predict an individual patient's pace of disease progression in non-idiopathic pulmonary fibrosis interstitial lung disease (non-IPF ILD) and identify which individuals will develop progressive pulmonary fibrosis.

Study Overview

• Status: Recruiting
• Conditions: Pulmonary Fibrosis
• Intervention / Treatment: Drug: [68Ga]CBP8; Drug: Gadoterate Meglumine

Detailed Description

60 participants with non-idiopathic pulmonary fibrosis interstitial lung disease (non-IPF ILD) on stable dose immunosuppression treatment will be enrolled. Participants will undergo combined [68Ga]CBP8 positron emission tomography (PET) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) at baseline. The investigators will compare the ability of PET and MRI measurements performed over the whole lung and within regions of interest to identify participants who subsequently develop progressive pulmonary fibrosis as determined by changes in pulmonary function testing, quantitative fibrosis on high-resolution computed tomography, and respiratory symptoms over 24 months. The investigators will also test whether combining the PET and MRI measurements results in more accurate prediction of progression than either modality alone.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sydney Montesi, MD; Phone Number: 617 724 4030; Email: sbmontesi@mgb.org
• Study Contact Backup: Name: Caroline Fromson; Phone Number: 617 643 3260; Email: cfromson@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Principal Investigator: Sydney Montesi, MD
      • Contact: Caroline Fromson; Phone Number: 617 643 3260; Email: cfromson@mgh.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18-80 with a diagnosis of chronic hypersensitivity pneumonitis, connective tissue-associated ILD (due to rheumatoid arthritis, systemic sclerosis, mixed connective tissue disease), or undifferentiated ILD.
2. On stable dose immunosuppression treatment (with prednisone, mycophenolate mofetil, mycophenolate sodium, and/or rituximab) for at least 3 months.
3. Pulmonary fibrosis, defined as honeycombing, traction bronchiectasis, or reticular opacities on HRCT performed within 1 year to or at Visit 1.
4. FVC of >/= 45% and DLCO >/= 25% predicted on PFTs performed at Visit 1.

Exclusion Criteria:

1. Current or prior exposure to FDA approved anti-fibrotic therapy.
2. Extent of emphysema greater than extent of fibrosis.
3. Pregnancy or plans to become pregnant at baseline or during follow-up.
4. Contraindications to MRI.
5. Contraindications to receiving gadolinium-based contrast agents.
6. Research-related radiation exposure exceeds 50 mSv in the prior year.
7. Estimated glomerular filtration rate (eGFR) < 30 mL/min (only for individuals with a history of chronic kidney disease).
8. Clinically significant PH defined by use of pulmonary vasodilatory therapy.
9. Respiratory infection within the prior 6 weeks.
10. Smoking of any kind within the prior 6 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Participants with Pulmonary Fibrosis; Participants with non-idiopathic pulmonary fibrosis interstitial lung disease (non-IPF ILD) will receive [68Ga]CBP8 and undergo PET combined with dynamic contrast-enhanced MRI	Drug: [68Ga]CBP8; Participants will receive a single intravenous injection of up to 350 MBq of [68Ga]CBP8; Drug: Gadoterate Meglumine; Participants will receive a single intravenous injection of 0.05 mmol/kg gadoterate meglumine during DCE-MRI; Other Names: Dotarem

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Development of progressive pulmonary fibrosis	Defined by the 2022 ATS guideline definition of progressive pulmonary fibrosis (PPF) which defines PPF as satisfying 2 of 3 criteria within 12 months: worsening symptoms, physiologic progression (absolute decline in FVC ≥ 5% or absolute decline in DLCO ≥ 10%), or radiologic evidence of disease progression.	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Decline of forced vital capacity (FVC) ≥ 5% from baseline	FVC will be measured at baseline, 6, 12, 18, and 24 months	Up to 24 months
Decline of forced vital capacity (FVC) ≥10% from baseline	FVC will be measured at baseline, 6, 12, 18, and 24 months	Up to 24 months
Decline of diffusing capacity for carbon monoxide (DLCO) ≥15% from baseline	DLCO will be measured at baseline, 6, 12, 18, and 24 months	Up to 24 months

Collaborators and Investigators

• Sponsor: Peter Caravan
• Investigators: Principal Investigator: Sydney Montesi, MD, Massachusetts General Hospital

Publications and helpful links

General Publications

• Montesi SB, Izquierdo-Garcia D, Desogere P, Abston E, Liang LL, Digumarthy S, Seethamraju R, Lanuti M, Caravan P, Catana C. Type I Collagen-targeted Positron Emission Tomography Imaging in Idiopathic Pulmonary Fibrosis: First-in-Human Studies. Am J Respir Crit Care Med. 2019 Jul 15;200(2):258-261. doi: 10.1164/rccm.201903-0503LE. No abstract available.
• Desogere P, Tapias LF, Hariri LP, Rotile NJ, Rietz TA, Probst CK, Blasi F, Day H, Mino-Kenudson M, Weinreb P, Violette SM, Fuchs BC, Tager AM, Lanuti M, Caravan P. Type I collagen-targeted PET probe for pulmonary fibrosis detection and staging in preclinical models. Sci Transl Med. 2017 Apr 5;9(384):eaaf4696. doi: 10.1126/scitranslmed.aaf4696.
• Izquierdo-Garcia D, Desogere P, Fur ML, Shuvaev S, Zhou IY, Ramsay I, Lanuti M, Catalano OA, Catana C, Caravan P, Montesi SB. Biodistribution, Dosimetry, and Pharmacokinetics of 68Ga-CBP8: A Type I Collagen-Targeted PET Probe. J Nucl Med. 2023 May;64(5):775-781. doi: 10.2967/jnumed.122.264530. Epub 2022 Dec 8.

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: July 29, 2024
• First Submitted That Met QC Criteria: July 29, 2024
• First Posted (Actual): August 1, 2024

Study Record Updates

• Last Update Posted (Actual): April 22, 2026
• Last Update Submitted That Met QC Criteria: April 17, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Interstitial; Fibrosis; Pathological Conditions, Signs and Symptoms; Pulmonary Fibrosis; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; gadoterate meglumine
• Other Study ID Numbers: 2024P001746

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No