PET/CT Scan with [18F]FP-R01-MG-F2 for Pulmonary Fibrosis

Overseen By Andrea Otte, DPT

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Stanford University

Disqualifiers: Pregnancy, Lung infection, Liver disease, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day per scan

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new imaging agent, [18F]FP-R01-MG-F2, to determine its effectiveness in detecting the protein Integrin avb6 in certain lung and liver conditions. It targets individuals with idiopathic pulmonary fibrosis (a lung disease), primary sclerosing cholangitis (a liver disease), and those who have or had COVID-19. The aim is to enhance disease detection using PET/CT scans, which are specialized body scans. Individuals diagnosed with these conditions and able to lie down for scans may be suitable candidates for this trial. As an Early Phase 1 trial, the research focuses on understanding how the imaging agent functions in people, offering participants the chance to be among the first to benefit from this innovative approach.

Do I need to stop my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications. Please consult with the study coordinators for more information.

What prior data suggests that this PET/CT scan with [18F]FP-R01-MG-F2 is safe?

In this study, researchers are using a substance called [18F]FP-R01-MG-F2. Specific safety information about this substance is not yet available because the trial is in its early stages. Early trials primarily focus on assessing the basic safety of a new treatment in people.

In similar studies, substances like [18F]FP-R01-MG-F2 are usually administered in small amounts and are generally considered safe. This particular substance is designed to attach to a protein called integrin avb6, found in some lung and liver conditions. As this is an early phase trial, the main goal is to ensure the substance's safety. Participants are closely monitored for any side effects during the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the use of [18F]FP-R01-MG-F2 in PET/CT scans because it offers a novel way to visualize and understand pulmonary fibrosis. Unlike traditional diagnostic methods that may not provide detailed insights into disease activity, this technique uses a radioactive tracer, [18F]FP-R01-MG-F2, which is specifically designed to highlight fibrotic tissue in the lungs. This approach could allow for more precise monitoring of disease progression and response to treatment. Additionally, the ability to use this imaging technique in specific patient groups, such as actively infected COVID-19 patients, PSC patients, and those with idiopathic pulmonary fibrosis (IPF), sets it apart from standard imaging methods and could lead to more tailored and effective management strategies.

What evidence suggests that this PET/CT scan is effective for detecting integrin avb6 in pulmonary fibrosis?

Research has shown that the tracer [18F]FP-R01-MG-F2 targets a protein called integrin αvβ6, which plays a role in diseases like idiopathic pulmonary fibrosis (IPF). This protein can trigger lung scarring. In this trial, participants will undergo [18F]FP-R01-MG-F2 PET/CT scans to help doctors identify where these proteins are active in the lungs, aiding in the understanding and management of IPF. This imaging tool enables doctors to pinpoint active areas of lung disease, which is crucial for planning treatment. Although still in early stages, these findings offer a promising way to monitor disease progression and treatment effectiveness. ^{2 5 6 7 8}

Who Is on the Research Team?

Henry Guo, MD, PhD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

This trial is for adults diagnosed with Idiopathic Pulmonary Fibrosis (IPF) or Primary Sclerosing Cholangitis (PSC), and those who have had COVID-19. Participants must be able to make informed decisions, follow study procedures, and meet specific health criteria like lung function tests. Pregnant individuals, those with certain other medical conditions or a recent history of cancer are excluded.

Inclusion Criteria

I have been diagnosed with large duct PSC based on specific liver tests.

I'm not sure what "Scanning Option C" refers to in this context. Can you provide more information or context?

Scanning Option A OR Scanning Option B

Exclusion Criteria

I have not had a lung infection in the last 3 months.

I had a lung condition like IPF or sarcoidosis before getting COVID-19.

I have a history of cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Administration of [18F]FP-R01-MG-F2 and PET/CT scans to assess integrin avb6 expression in IPF, PSC, and COVID-19 patients

1 day per scan

1 visit (in-person) per scan

Follow-up

Participants may have a repeat [18F]FP-R01-MG-F2 PET/CT scan performed within 3-8 weeks post initial scan

3-8 weeks

Long-term follow-up

IPF patients may have a repeat scan within 12-24 months post initial scan if willing to be re-consented

12-24 months

What Are the Treatments Tested in This Trial?

Interventions

• [18F]FP-R01-MG-F2

Trial Overview [18F]FP-R01-MG-F2 is being tested using PET/CT scans to detect Integrin avb6 in patients with IPF, PSC, or COVID-19. The study aims to understand how this imaging agent can help visualize disease processes in these conditions.

How Is the Trial Designed?

Group I: [18F]FP-R01-MG-F2 PET/CT in actively infected COVID19 Patients Experimental Treatment 1 Intervention

Arm 3: 7mCi (range 6-9 mCi) \[18F\]FP-R01-MG-F2 will be administered to the study participant. One vertex-to-thigh PET/CT scans to the center of the lung in the FOV will follow approximately 60 min post-injection.

Group II: [18F]FP-R01-MG-F2 PET/CT in PSC Patients Experimental Treatment 1 Intervention

Arm 2: 7mCi (range 6-9 mCi) \[18F\]FP-R01-MG-F2 will be administered to the study participant. A 60-minute dynamic PET/CT scan to the center of the liver in the FOV is followed by two vertex-to-thigh PET/CT scans. Patients will have the option for a repeat \[18F\]FP-R01-MG-F2 PET/CT scan performed within 3-8 weeks post initial scan.

Group III: [18F]FP-R01-MG-F2 PET/CT in IPF Patients, Recovered COVID19 Patients, and Healthy Volunteers Experimental Treatment 1 Intervention

Arm1: 7mCi (range 6-9 mCi) \[18F\]FP-R01-MG-F2 will be administered to the study participant. A 60-minute dynamic PET/CT scan to the center of the lungs in the FOV is followed by two vertex-to-thigh PET/CT scans. NOTE: If the patient cannot tolerate lying down for an extended period of time at the time of imaging, the patient may be switched to scanning protocol Option B, which does not include an initial 60-minute dynamic PET/CT scan. IPF Patients will have a repeat \[18F\]FP-R01-MG-F2 PET/CT scan performed within 3-8 weeks post initial scan (within 12-24 months post initial scan for previously scanned IPF patients if they are willing to be re-consented).

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Pliant Therapeutics, Inc.

Industry Sponsor

Trials

8

Recruited

720+

Published Research Related to This Trial

The automated synthesis of the PET radiotracer [18F]mG4P027 for metabotropic glutamate receptor 4 (mGluR4) was successfully developed, ensuring high purity and yield, which is crucial for future human studies.

This advancement in automation addresses previous challenges in the manual synthesis process, making it more efficient and reliable for potential clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fully Automated Radiosynthesis of [18F]mG4P027 for mGluR4 Imaging. Moon, SH., El Fakhri, G., Zhang, Z., et al.[2023]

Whole body positron emission tomography (PET) using F-18 FDG can help identify metabolically active areas in idiopathic pulmonary fibrosis (IPF), which may indicate regions that could respond to treatment.

The imaging technique revealed not only active disease in the lungs but also potential extrapulmonary involvement, highlighting the complexity of IPF and the need for comprehensive diagnostic approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography in idiopathic pulmonary fibrosis: A new ray of hope! Desai, U., Karkhanis, VS., Basu, S., et al.[2020]

The newly developed radiotracer [18 F]-(E)-PSS232 shows high binding affinity for the mGlu5 receptor, making it a promising tool for visualizing this receptor in the brain, which is important for studying neuropsychiatric disorders.

The automated synthesis of [18 F]2a achieved a reliable radiochemical yield of 40% and high purity (>95%), allowing for efficient production and distribution for clinical use, with a total synthesis time of just 70 minutes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Automated cGMP-compliant radiosynthesis of [18 F]-(E)-PSS232 for brain PET imaging of metabotropic glutamate receptor subtype 5. Park, JY., Son, J., Yun, M., et al.[2019]

Hypoxia imaging using [18F]FMISO can serve as an early predictive biomarker for disease progression in idiopathic pulmonary fibrosis (IPF), showing changes before they are visible on traditional CT scans.

Both nintedanib and pirfenidone significantly reduced lung fibrosis and hypoxia markers, indicating their efficacy in treating IPF, with [18F]FMISO uptake correlating with the effectiveness of nintedanib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[18F]FMISO PET/CT imaging of hypoxia as a non-invasive biomarker of disease progression and therapy efficacy in a preclinical model of pulmonary fibrosis: comparison with the [18F]FDG PET/CT approach. Tanguy, J., Goirand, F., Bouchard, A., et al.[2022]

The study evaluated the safety and efficacy of a new imaging agent, 99mTc-HFAPI, in 11 patients with idiopathic pulmonary fibrosis (IPF), showing no side effects and normal physiological uptake in organs like the liver and pancreas.

99mTc-HFAPI imaging demonstrated elevated uptake in fibrotic lung regions, correlating significantly with disease severity on high-resolution CT scans and pulmonary function test results, suggesting its potential for monitoring disease progression in IPF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

99mTc-Labeled FAPI SPECT Imaging in Idiopathic Pulmonary Fibrosis: Preliminary Results. Liu, Y., Zhang, Q., Zhang, Y., et al.[2023]

The newly developed PET ligand [(18) F]FPIT effectively binds to metabotropic glutamate receptor type 1 (mGluR1) in rat and monkey brains, showing high specific binding in areas like the cerebellum and thalamus, which is crucial for accurate imaging.

In vivo PET studies demonstrated that [(18) F]FPIT has high brain uptake and distribution patterns consistent with its binding profile, indicating its potential for visualizing mGluR1 expression in human brains.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of 1-(2-[18F] fluoro-3-pyridyl)-4-(2-isopropyl-1-oxo- isoindoline-5-yl)-5-methyl-1H-1,2,3-triazole, a PET ligand for imaging the metabotropic glutamate receptor type 1 in rat and monkey brains. Fujinaga, M., Maeda, J., Yui, J., et al.[2018]

FAPI PET imaging using [68Ga]Ga-FAPI-46 was able to detect increased lung uptake in a mouse model of pulmonary fibrosis at both 7 and 14 days post-bleomycin administration, indicating its potential as a biomarker for disease activity.

In contrast, traditional CT imaging only identified differences in fibrosis at 14 days, highlighting FAPI PET's superior ability to assess early disease activity and response to treatment in idiopathic pulmonary fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[68&#160;Ga]Ga-FAPI-46 PET for non-invasive detection of pulmonary fibrosis disease activity. Rosenkrans, ZT., Massey, CF., Bernau, K., et al.[2022]

This study successfully measured the in vivo affinity and density of the metabotropic glutamate receptor subtype 1 (mGluR1) in rat brains using a new PET ligand, (18)F-FITM, providing valuable insights into its role in central nervous system disorders.

The results showed a high correlation between the binding potentials obtained from the noninvasive equilibrium analysis and invasive methods, indicating that (18)F-FITM can effectively be used to study mGluR1 functions and aid in the development of new treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo measurement of the affinity and density of metabotropic glutamate receptor subtype 1 in rat brain using 18F-FITM in small-animal PET. Yamasaki, T., Fujinaga, M., Kawamura, K., et al.[2016]

In a study of 113 idiopathic pulmonary fibrosis (IPF) patients, a high pulmonary target-to-background ratio (TBR) from 18F-FDG-PET/CT scans was found to be independently associated with an increased risk of mortality, indicating its potential as a prognostic biomarker.

The study demonstrated that combining the TBR with the established GAP scoring system improved the prediction of mortality in IPF patients, suggesting that this 'PET modified GAP score' could enhance risk stratification for better patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary 18F-FDG uptake helps refine current risk stratification in idiopathic pulmonary fibrosis (IPF). Win, T., Screaton, NJ., Porter, JC., et al.[2018]

The study developed a new PET radiotracer, (E)-[(18)F]-16, which showed excellent binding affinity for the mGluR5 receptor with a K(d) of 70 nM, indicating its potential effectiveness for imaging this receptor subtype.

In vitro studies demonstrated that (E)-[(18)F]-16 has high specificity for mGluR5, making it a promising candidate for further research in neuroimaging applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and evaluation of novel α-fluorinated (E)-3-((6-methylpyridin-2-yl)ethynyl)cyclohex-2-enone-O-methyl oxime (ABP688) derivatives as metabotropic glutamate receptor subtype 5 PET radiotracers. Milicevic Sephton, S., Mu, L., Schweizer, WB., et al.[2016]

The study demonstrated that [68 Ga]Ga-FAPI-04 PET/CT can effectively detect early cardiac fibrosis in rats with pressure overload heart failure, showing increased accumulation of the tracer in the heart over time, which correlated with worsening cardiac function.

The findings suggest a significant link between cardiac and liver fibrosis, as indicated by the correlation of PET signals in both organs, highlighting the potential of [68 Ga]Ga-FAPI-04 PET/CT in predicting the prognosis of nonischemic heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular imaging of fibroblast activity in pressure overload heart failure using [68&#160;Ga]Ga-FAPI-04 PET/CT. Wang, G., Yang, Q., Wu, S., et al.[2023]

In a study of 50 patients with idiopathic pulmonary fibrosis (IPF), a positive retention index value (RI-SUV) from dual-time-point (18)F-FDG PET imaging was found to be a strong predictor of shorter progression-free survival, with a median of 13.3 months compared to 27.9 months for those with negative RI-SUV.

The study also revealed that a positive RI-SUV is associated with significantly higher mortality rates, with a 5-year survival rate of only 14.3% for patients with positive RI-SUV compared to 76.8% for those with negative RI-SUV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic Value of Dual-Time-Point 18F-FDG PET for Idiopathic Pulmonary Fibrosis. Umeda, Y., Demura, Y., Morikawa, M., et al.[2016]

Citations

1. atsjournals.org atsjournals.org/doi/pdf/10.1513/AnnalsATS.202409-969OC?download=true

Bexotegrast Shows Dose-Dependent Integrin ... The primary objective was to evaluate αvß6 receptor occupancy by bexotegrast as assessed by changes from baseline in. [18F]FP-R01-MG-F2 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7075837/

Clinical quantification of the integrin αvβ6 by [18F]FB ... The RGD-integrin, αvβ6, plays a role in the pathogenesis of pulmonary fibrosis through activation of transforming growth factor beta (TGFβ).

3. pliantrx.com pliantrx.com/wp-content/uploads/2024/11/Mooney-et-al.-2024-Bexotegrast-shows-dose-dependent-integrin-%CE%B1v%CE%B26r-receptor-occupancy-in-lungs-of-participants-with-IPF.pdf

Bexotegrast Shows Dose-dependent Integrin αvβ6 ... In a Phase 2 study of participants with IPF, bexotegrast showed a favorable safety profile up to 40 weeks of treatment, and showed improved lung ...

4. d-nb.info d-nb.info/1212107349/34

A positron emission tomography imaging study to confirm ... PET ligand ([18F]FP-R01-MG-F2) [11]. The aim of this study was to evaluate the safety, toler- ability and PK of GSK3008348 in participants with IPF and to ...

5. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/15/NCT04072315/Prot_000.pdf

CLINICAL TRIAL PROTOCOL PLN-74809-IPF-201 Pliant Therapeutics Inc is developing PLN-74809-000 (hereafter referred to as PLN-74809) for the treatment of idiopathic pulmonary fibrosis (IPF) ...

6. stanfordhealthcare.org stanfordhealthcare.org/publications/925/925961.html

A Phase 2, Open-Label Clinical Trial. ... ([18F]FP-R01-MG-F2). avß6 receptor occupancy by bexotegrast was estimated from the changes in PET tracer uptake following bexotegrast. Pharmacokinetics ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7099768/

A positron emission tomography imaging study to confirm ... This study evaluated the safety, pharmacokinetics (PK) and target engagement in the lungs, of GSK3008348, a novel inhaled alpha-v beta-6 (αvβ6) integrin ...

8. withpower.com withpower.com/trial/early-phase-1-idiopathic-pulmonary-fibrosis-10-2017-ce3f8?lat=34.60184&lng=-117.81218

PET/CT Scan with [18F]FP-R01-MG-F2 for Pulmonary ... The provided research does not contain any safety data for [18F]FP-R01-MG-F2 or its variants. The studies focus on different radiotracers for imaging ...