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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new imaging tool called [68Ga]CBP8, a collagen-targeted imaging agent, to evaluate its effectiveness in detecting early signs of interstitial lung disease. This condition causes lung tissue to scar, making breathing difficult. Participants will receive this imaging agent and undergo a special scan to detect collagen buildup in the lungs. Individuals with early-stage lung issues or a family history of pulmonary fibrosis might be suitable candidates, especially if they haven't smoked recently. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants the opportunity to contribute to advancements in early lung disease detection.

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 prior data suggests that [68Ga]CBP8 is safe for detecting collagen deposition in interstitial lung disease?

Research has shown that [68Ga]CBP8 has been tested in humans to ensure its safety and effectiveness for detecting collagen in the lungs. This is crucial for conditions like pulmonary fibrosis, where lung scarring occurs. Studies indicate that this probe can identify increased collagen in the lungs of individuals with idiopathic pulmonary fibrosis compared to healthy individuals.

Regarding safety, [68Ga]CBP8 is in Phase 2 trials, meaning it has passed initial safety tests and is now being examined more closely for both safety and effectiveness. Although detailed safety data is limited, its Phase 2 status suggests it is generally well-tolerated.

Dotarem, a contrast agent commonly used in MRI scans to enhance image clarity, is generally considered safe when used as directed. Since Dotarem is already FDA-approved for other uses, it has passed safety evaluations for those conditions.

Overall, both [68Ga]CBP8 and Dotarem have been studied for safety, with Dotarem having a long history of use. While more data is always beneficial, current findings suggest these treatments are safe for human use in the context being studied. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores a new imaging technique that targets collagen in the lungs, using a compound called [68Ga]CBP8. This approach is different because it aims to provide a more precise picture of lung abnormalities, like interstitial lung disease (ILD), compared to traditional imaging methods. By using PET-MRI with [68Ga]CBP8, doctors hope to better understand the extent and progression of lung conditions, potentially leading to more tailored and effective treatments in the future.

What evidence suggests that [68Ga]CBP8 is effective for detecting collagen deposition in interstitial lung disease?

Research has shown that \[68Ga\]CBP8 effectively detects increased collagen in the lungs of individuals with idiopathic pulmonary fibrosis, a type of lung disease. Studies found that patients with fibrosis absorbed this substance significantly more than healthy individuals. This indicates its ability to identify areas with increased collagen, signaling fibrosis or lung scarring. In animal tests, \[68Ga\]CBP8 effectively tracked collagen levels, suggesting potential effectiveness in humans. In this trial, participants with interstitial lung abnormalities or interstitial lung disease, along with first-degree relatives of individuals with pulmonary fibrosis, will receive \[68Ga\]CBP8 and undergo PET-MRI. Early results suggest that this imaging method could improve the identification and understanding of lung diseases. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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 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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03535545

Preliminary Evaluation of [68Ga]CBP8 in Healthy ... The goal of this study is to investigate the safety of [68Ga]CBP8 and its efficacy to detect collagen deposition in pulmonary fibrosis. Detailed Description.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5568793/

Type I collagen-targeted PET probe for pulmonary fibrosis ... Data show significantly higher uptake of 68Ga-CBP8 in lungs of LDBVL animals ... Probe 68Ga-CBP8 allows monitoring of collagen content in human IPF lung samples.

3. researchgate.net researchgate.net/publication/366151768_Biodistribution_Dosimetry_and_Pharmacokinetics_of_68_Ga-CBP8_A_type_I_collagen_targeted_PET_probe

A Type I Collagen–Targeted PET Probe | Request PDF The 68Ga-Collagen Binding Probe #8, 68Ga-CBP8, is a peptide-based, type I collagen-targeted probe developed for imaging of tissue fibrosis.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10152126/

Biodistribution, Dosimetry, and Pharmacokinetics of 68Ga ... In humans, this probe detected increased collagen in the lungs of those with idiopathic pulmonary fibrosis compared with healthy volunteers (9).

5. withpower.com withpower.com/trial/phase-2-lung-diseases-interstitial-6-2022-23240

Collagen-targeted PET Imaging 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 ...

6. jnm.snmjournals.org jnm.snmjournals.org/content/64/5/775

Biodistribution, Dosimetry, and Pharmacokinetics of 68Ga-CBP8 In humans, this probe detected increased collagen in the lungs of those with idiopathic pulmonary fibrosis compared with healthy volunteers (9).