Advanced Imaging to Assess the Effect of Immunosuppression on Progressive Fibrosis

Advanced Imaging to Assess the Effect of Immunosuppression on Progressive Lung Fibrosis in Participants With Non-Idiopathic Pulmonary Fibrosis Interstitial Lung Disease

The purpose of this study is to investigate how immunosuppression treatment affects measurements of active collagen deposition using [68Ga]CBP8 positron emission tomography (PET) and tissue injury using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in individuals with non-idiopathic pulmonary fibrosis interstitial lung disease (non-IPF ILD).

Study Overview

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

Detailed Description

15 different subjects with non-IPF ILD starting immunosuppression treatment for their underlying ILD will be enrolled. Participants will undergo [68Ga]CBP8 PET and DCE-MRI prior to and 12 weeks after treatment initiation to determine the effects of immunosuppressive treatment on PET measurements of collagen deposition and selected DCE-MRI-derived measurements.

• Study Type: Interventional
• Enrollment (Estimated): 15
• 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: Sydney Montesi; 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. Starting immunosuppression treatment with mycophenolate mofetil, mycophenolate sodium, and / or prednisone for clinically indicated non-IPF ILD treatment.
3. Pulmonary fibrosis, defined as honeycombing, traction bronchiectasis, or reticular opacities on high-resolution computed tomography (HRCT) performed within 1 year to or at Visit 1.
4. Forced vital capacity (FVC) of >/= 45% and diffusing capacity of the lungs for carbon monoxide (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 millisievert (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 pulmonary hypertension (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 prior to and 12 weeks after starting clinically-prescribed immunosuppression for treatment of non-IPF ILD	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in SUVmax25 over the entire lungs	Changes in lung collagen uptake will be measured using the PET probe [68]Ga-CBP8. Measurements will be made using the mean of the upper quartile of standardized uptake values (SUVmax25). Primary [68Ga]CBP8-PET outcome.	From baseline to 12 weeks
Change in the rate of contrast washin (kwashin) over the entire lungs	Changes in rate of contrast washin will be measured using dynamic-contrast enhanced MRI. Primary DCE-MRI outcomes.	From baseline to 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in SUVmean over the entire lungs	Changes in lung collagen uptake will be measured using the PET probe [68]Ga-CBP8. Measurements will be made using the mean standardized uptake value (SUVmean).	From baseline to 12 weeks
Change in SUVmax over the entire lungs	Changes in lung collagen uptake will be measured using the PET probe [68]Ga-CBP8. Measurements will be made using the max standardized uptake value (SUVmax).	From baseline to 12 weeks
Change in peak enhancement over the entire lungs	Changes in peak enhancement will be measured using dynamic-contrast enhanced MRI	From baseline to 12 weeks
Change in time to peak over the entire lungs	Changes in time to peak will be measured using dynamic-contrast enhanced MRI	From baseline to 12 weeks
Change in the area under the curve at 60 seconds (AUC60) over the entire lungs	Changes in the area under the curve at 60 seconds will be measured using dynamic-contrast enhanced MRI	From baseline to 12 weeks
Change in the rate of contrast washout (kwashout) over the entire lungs	Changes in the rate of contrast washout will be measured using dynamic-contrast enhanced MRI.	From baseline to 12 weeks

Collaborators and Investigators

• Sponsor: Peter Caravan
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• 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 (Estimated): April 1, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: April 17, 2026
• First Submitted That Met QC Criteria: May 2, 2026
• First Posted (Actual): May 7, 2026

Study Record Updates

• Last Update Posted (Actual): May 7, 2026
• Last Update Submitted That Met QC Criteria: May 2, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Fibrosis; Pathological Conditions, Signs and Symptoms; Pulmonary Fibrosis; Lung Diseases, Interstitial; gadoterate meglumine
• Other Study ID Numbers: 2024P001746Aim3; R01HL171240 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No