Collagen-targeted PET Imaging for Interstitial Lung Disease

Overseen By Abimbola Akinniyi

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Massachusetts General Hospital

Disqualifiers: Electrical implants, Ferromagnetic implants, Low eGFR, Pregnancy, Claustrophobia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

30 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the drug 68Ga-CBP8 for interstitial lung disease?

Research shows that 68Ga-CBP8 is effective in detecting pulmonary fibrosis (scarring of the lungs) in animal models and correlates well with the amount of lung collagen, which is a key feature of fibrosis. This suggests it could be useful for noninvasive imaging of lung fibrosis in humans. ^{1 2 3 4 5}

Is the collagen-targeted PET imaging treatment safe for humans?

The safety of gadoterate meglumine (also known as Dotarem) has been evaluated in various studies, showing no significant safety concerns even in individuals with kidney issues. Additionally, a study involving 22,897 examinations found no symptoms of potential gadolinium toxicity, suggesting it is generally safe for human use. ^{6 7 8 9 10}

How does the collagen-targeted PET imaging treatment differ from other treatments for interstitial lung disease?

This treatment is unique because it uses a special imaging technique called PET (positron emission tomography) to target and visualize collagen in the lungs, which is a key marker of fibrosis (scarring). Unlike traditional treatments that focus on managing symptoms, this approach helps in early detection and monitoring of lung fibrosis by providing a noninvasive way to see the extent of collagen buildup. ^{1 2 3 4 5}

What is the purpose of this trial?

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

Eligibility Criteria

This trial is for people over 40 years old with early signs of interstitial lung disease (ILD) or those without ILD but have a relative with pulmonary fibrosis. Participants should not have used tobacco in the last 6 months, be pregnant, or have certain metal implants and allergies to gadolinium. They must also be able to lie comfortably in an MR-PET scanner.

Inclusion Criteria

I am over 40 years old.

I have never had interstitial lung disease.

My lung condition shows early signs of scarring but not a specific severe pattern.

Exclusion Criteria

I have a lung condition that is not ILD/ILAs or emphysema.

I have not had pneumonia or a serious lung infection in the last 6 weeks.

I have had radiation therapy to my chest area before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants receive [68Ga]CBP8 and undergo PET-MRI to assess collagen deposition in the lungs

1-2 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging

24 months

Treatment Details

Interventions

• [68Ga]CBP8
• Dotarem

Trial Overview The study tests [68Ga]CBP8's ability to detect collagen in lungs affected by early ILD using PET imaging. It compares this new method against Dotarem, a standard contrast agent, to see which better identifies early disease stages.

Participant Groups

Group I: Subjects with interstitial lung abnormalities (ILAs) or interstitial lung disease (ILD) Experimental Treatment 2 Interventions

Subjects with interstitial lung abnormalities (ILAs) or interstitial lung disease (ILD) will receive \[68Ga\]CBP8 and undergo PET-MRI.

Group II: First degree relatives of a family member with pulmonary fibrosis Experimental Treatment 2 Interventions

First degree relatives of a family member with pulmonary fibrosis will receive \[68Ga\]CBP8 and undergo PET-MRI.

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Boehringer Ingelheim

Industry Sponsor

Trials

2,566

Recruited

16,150,000+

Findings from Research

CBP1495 is a newly identified collagen-binding peptide that effectively targets collagen type I, showing strong binding affinity and potential for use in imaging fibrosis.

The 99mTc-labelled version of CBP1495 demonstrated significant accumulation in fibrotic tissues in rat models, indicating its potential as a non-invasive radiotracer for diagnosing and monitoring fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular imaging of fibrosis using a novel collagen-binding peptide labelled with 99mTc on SPECT/CT. Zheng, L., Ding, X., Liu, K., et al.[2018]

The developed probe, [68Ga]Ga·DOTA-CMP, effectively detects abnormal collagen in the lungs of a mouse model of idiopathic pulmonary fibrosis (IPF), indicating its potential for early diagnosis of the disease.

This probe shows high selective uptake in fibrotic lung tissue with minimal background signal in other organs, suggesting it could be a safe and effective tool for identifying IPF at an earlier stage when treatment may be more beneficial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of Pulmonary Fibrosis with a Collagen-Mimetic Peptide. Borgula, IM., Shuvaev, S., Abston, E., et al.[2023]

The 68Ga-Collagen Binding Probe #8 (68Ga-CBP8) was safely administered to nine healthy volunteers, showing no adverse effects and demonstrating favorable biodistribution with rapid renal clearance.

This probe has potential for noninvasive imaging of tissue fibrosis, with pharmacokinetics indicating a quick initial distribution and a longer elimination phase, making it suitable for assessing fibrotic diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biodistribution, Dosimetry, and Pharmacokinetics of 68Ga-CBP8: A Type I Collagen-Targeted PET Probe. Izquierdo-Garcia, D., Désogère, P., Fur, ML., et al.[2023]

The peptide-based PET probe 68Ga-CBP8 specifically targets collagen type I and shows high specificity for pulmonary fibrosis in a mouse model, indicating its potential for noninvasive imaging of this condition.

In vivo and ex vivo studies demonstrated a strong correlation between 68Ga-CBP8 uptake and lung collagen levels, suggesting it could effectively monitor treatment responses in pulmonary fibrosis patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Type I collagen-targeted PET probe for pulmonary fibrosis detection and staging in preclinical models. Désogère, P., Tapias, LF., Hariri, LP., et al.[2018]

The study developed a collagen-targeted PET probe, 64Cu-CBP7, which showed significantly higher uptake in the lungs of mice with bleomycin-induced pulmonary fibrosis compared to healthy controls, indicating its potential for early detection of lung fibrosis.

64Cu-CBP7 demonstrated superior metabolic stability and specificity for collagen, making it a promising candidate for noninvasive imaging of pulmonary fibrosis progression in vivo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimization of a Collagen-Targeted PET Probe for Molecular Imaging of Pulmonary Fibrosis. Désogère, P., Tapias, LF., Rietz, TA., et al.[2020]

Gadoterate meglumine (Gd-DOTA) demonstrated a diagnostic efficacy of over 99% in establishing diagnoses during MRI scans in a study involving 24,308 patients across 61 institutions.

The safety profile of Gd-DOTA was favorable, with only 0.4% of patients experiencing adverse events, mostly minor, and only one serious event reported, which resulted in complete recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical safety and diagnostic value of the gadolinium chelate gadoterate meglumine (Gd-DOTA). Herborn, CU., Honold, E., Wolf, M., et al.[2022]

In a study of 22,897 contrast-enhanced MRI scans, gadoteric acid (Dotarem®) showed no significant association with symptoms of gadolinium toxicity, even in patients with renal insufficiency, suggesting it is a safe option for these patients.

There were zero reported cases of nephrogenic systemic fibrosis (NSF) among 3,209 administrations of gadoteric acid to patients with renal insufficiency, and only 0.01% experienced hypersensitivity reactions, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Absence of potential gadolinium toxicity symptoms following 22,897 gadoteric acid (Dotarem®) examinations, including 3,209 performed on renally insufficient individuals. Young, LK., Matthew, SZ., Houston, JG.[2021]

Gadolinium (Gd) was found to deposit in brain and bone tissues of patients with normal renal function who received non-Group 1 Gd-based contrast agents, indicating that even these agents can lead to Gd accumulation in the body.

Bone tissue showed significantly higher levels of Gd compared to brain tissue, suggesting that bone could potentially be used as a marker to estimate Gd levels in the brain for clinical or research purposes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Macrocyclic and Other Non-Group 1 Gadolinium Contrast Agents Deposit Low Levels of Gadolinium in Brain and Bone Tissue: Preliminary Results From 9 Patients With Normal Renal Function. Murata, N., Gonzalez-Cuyar, LF., Murata, K., et al.[2018]

In a phase 3 study involving 273 participants, gadopiclenol at a lower dose (0.05 mmol/kg) was found to be noninferior to gadobutrol at a higher dose (0.1 mmol/kg) for visualizing lesions in body MRI, indicating it can be an effective alternative.

Both gadopiclenol and gadobutrol showed similar safety profiles, with no significant differences in adverse events, suggesting that gadopiclenol may provide a safer option with a reduced gadolinium dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Half-Dose Gadopiclenol versus Full-Dose Gadobutrol for Contrast-enhanced Body MRI. Kuhl, C., Csőszi, T., Piskorski, W., et al.[2023]

Gd-BOPTA, a lower-dose contrast agent, can be used effectively in delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) at half the dose of Gd-DTPA, showing similar T1-values and contrast penetration in healthy cartilage.

In patients with knee pain, Gd-BOPTA demonstrated higher T1-values compared to Gd-DTPA, but both agents equally detected areas of cartilage damage, suggesting Gd-BOPTA is a safe and effective alternative with reduced risk of nephrogenic systemic fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of using half-dose Gd-BOPTA for delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) at the knee, compared with standard-dose Gd-DTPA. Rehnitz, C., Do, T., Klaan, B., et al.[2021]

References

1. Austria pubmed.ncbi.nlm.nih.gov

Molecular imaging of fibrosis using a novel collagen-binding peptide labelled with 99mTc on SPECT/CT. [2018]

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

Detection of Pulmonary Fibrosis with a Collagen-Mimetic Peptide. [2023]

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

Biodistribution, Dosimetry, and Pharmacokinetics of 68Ga-CBP8: A Type I Collagen-Targeted PET Probe. [2023]

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

Type I collagen-targeted PET probe for pulmonary fibrosis detection and staging in preclinical models. [2018]

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

Optimization of a Collagen-Targeted PET Probe for Molecular Imaging of Pulmonary Fibrosis. [2020]

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

Clinical safety and diagnostic value of the gadolinium chelate gadoterate meglumine (Gd-DOTA). [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Absence of potential gadolinium toxicity symptoms following 22,897 gadoteric acid (Dotarem®) examinations, including 3,209 performed on renally insufficient individuals. [2021]

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

Macrocyclic and Other Non-Group 1 Gadolinium Contrast Agents Deposit Low Levels of Gadolinium in Brain and Bone Tissue: Preliminary Results From 9 Patients With Normal Renal Function. [2018]

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

Efficacy and Safety of Half-Dose Gadopiclenol versus Full-Dose Gadobutrol for Contrast-enhanced Body MRI. [2023]

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

Feasibility of using half-dose Gd-BOPTA for delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) at the knee, compared with standard-dose Gd-DTPA. [2021]