FAPI-74 PET/CT for Fibrosis

Overseen By Mary Hansbury

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Abramson Cancer Center at Penn Medicine

Must not be taking: Corticosteroids, Systemic investigational agents

Disqualifiers: Pregnancy, Active TB, Alternative pulmonary 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

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new imaging method called FAPI-74 PET/CT to assess its effectiveness in detecting fibrosis, which is unwanted tissue scarring, in the body. Fibrosis can occur in various conditions such as head and neck cancer, post-tuberculosis lung disease, and cardiac sarcoidosis. The imaging aims to enhance understanding of how these conditions affect the body and potentially lead to better treatments. Individuals with medical conditions known or suspected to cause fibrosis might be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to benefit from this innovative approach.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are in the PTLD cohort, you should not have taken corticosteroids or other systemic investigational agents within 3 months of screening.

What prior data suggests that this protocol is safe for imaging fibrosis?

Research has shown that [F-18]-FAPI-74 has been studied primarily for imaging cancer, and patients generally tolerated it well. Few reports of serious side effects suggest it is likely safe.

Currently, this treatment is in early clinical trials to determine its effectiveness in imaging fibrosis. Researchers are still gathering detailed safety information. The fact that it is being tested in people indicates that earlier tests did not reveal major safety concerns. Additionally, previous studies for other uses did not identify significant issues, which bodes well for its application in this new area. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about [F-18]-FAPI-74 because it offers a new way to detect and visualize tissue fibrosis using a PET/CT scan. Unlike traditional imaging methods that may not effectively highlight fibrotic tissue, FAPI-74 targets fibroblast activation protein (FAP), which is often overexpressed in fibrotic conditions. This targeted approach could provide clearer, more precise images, allowing doctors to better understand the extent and activity of fibrosis in various conditions like cancer or post-infection scenarios. This has the potential to significantly improve diagnosis and treatment planning.

What evidence suggests that this protocol is effective for imaging fibrosis?

Research has shown that [F-18]-FAPI-74, the investigational imaging agent used in this trial, is a promising tool for imaging fibrosis, the scarring of tissue often caused by various medical conditions. Early results indicate that this imaging method effectively detects scarred changes in the lungs of patients with idiopathic pulmonary fibrosis, a lung disease. Studies also suggest that FAPI-74 may surpass traditional methods in identifying primary tumors and cancer recurrences. It targets a protein called fibroblast activation protein, often found in high amounts in scarred and cancerous tissues. While researchers continue to study this technique, these early findings suggest it could effectively identify fibrosis in different conditions. ^{3 6 7 8 9}

Who Is on the Research Team?

Mark Sellmyer, M.D. Ph.D.

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

This trial is for adults with medical conditions that lead to fibrosis or scarring. Specific eligibility criteria are not provided, but typically participants must have a condition where fibrosis is known to cause health issues and poor outcomes.

Inclusion Criteria

I am over 21, have oropharyngeal cancer, and can undergo surgery.

All Cohorts: History of known or suspected fibrosis-inducing medical condition, Participants must be informed of the investigational nature of this study and be willing to provide written informed consent and participate in this study in accordance with institutional and federal guidelines prior to study-specific procedures.

I am over 21, cured of TB as per guidelines, with no recent positive TB cultures.

Exclusion Criteria

My head or neck cancer cannot be removed with surgery.

PTLD Cohort: Diagnosed with TB that is resistant to rifampin, History of alternative pulmonary disease, Have been administered corticosteroids or any other systemic investigational agents within 3 months of screening, Have symptoms or signs suggestive of active TB at the time of screening

All Cohorts: Women of childbearing potential may not be pregnant or breastfeeding. A negative pregnancy test will be required before [F-18]- FAPI-74 injection, Inability to tolerate imaging procedures in the opinion of an investigator or treating physician, Any current medical condition, illness, or disorder as assessed by medical record review and/or self-reported that is considered by a physician investigator to be a condition that could compromise participant safety or successful participation in the study, Treatment with a therapeutic agent targeting fibroblast activation protein (FAP) within 1 month prior to study enrollment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants undergo a PET/CT scan using [F-18]-FAPI-74 to evaluate the distribution of fibroblast activating protein (FAP) in major organs and tissues affected by fibrotic diseases.

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in fibrosis over time, with optional second PET/CT scans to quantify changes in FAP uptake.

3 years

What Are the Treatments Tested in This Trial?

Interventions

• [F-18]-FAPI-74

Trial Overview [F-18]-FAPI-74 PET/CT scans are being tested in this study. The goal is to see how well they can image and detect the presence of fibrosis across various diseases where scarring adversely affects health.

How Is the Trial Designed?

Group I: FAPI-74 PET/CT Scan Experimental Treatment 1 Intervention

Head and neck cancer (up to 15 subjects), post tubercular lung disease (PTLD, up to 10 subjects), Cardiac Sarcoidosis and Exploratory (up to 10 subjects each) with fibrosis-inducing medical conditions that are known or suspected to cause tissue fibrosis (e.g. cancer-associated, postinfection, post-radiation, pre/post-transplant, cardiac, liver, kidney or pulmonary fibrosis).

[F-18]-FAPI-74 is already approved in United States for the following indications:

Approved in United States as [18F]FAPI-74 for:

• Investigational use for diagnosis of gastrointestinal cancers, including hepatocellular carcinoma, cholangiocarcinoma, gastric, pancreatic, and colorectal cancer

Who Is Running the Clinical Trial?

Abramson Cancer Center at Penn Medicine

Lead Sponsor

Trials

425

Recruited

464,000+

Published Research Related to This Trial

A total of 294 publications on fibroblast activation protein inhibitor (FAPI) imaging and therapy were identified, with 71% being case reports and 29% cohort studies, indicating a strong focus on diagnostic imaging in various cancers and benign diseases.

Preliminary findings from 16 studies on radionuclide therapy suggest acceptable toxicity profiles and potential for disease control, highlighting the need for more rigorous, prospective studies to better understand the clinical applications of FAPI theranostics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current research topics in FAPI theranostics: a bibliometric analysis. van den Hoven, AF., Keijsers, RGM., Lam, MGEH., et al.[2023]

FAPI PET/CT imaging shows promise as a molecular imaging tool in oncology, potentially outperforming traditional 18F-FDG PET/CT for certain cancers, based on a review of preclinical and clinical studies.

The technique's potential as a theranostic tool, which combines therapy and diagnostics, highlights its future importance, although more research and clinical trials are needed to fully establish its efficacy and applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fibroblast Activation Protein Inhibitor PET/CT: A Promising Molecular Imaging Tool. Sharma, P., Singh, SS., Gayana, S.[2023]

The novel 18F-labeled FAP inhibitor, [18F]AlF-FAPT, shows improved imaging capabilities for abdominal tumors compared to the previously used [18F]FAPI-42, due to its lower hepatobiliary uptake.

[18F]AlF-FAPT can be synthesized quickly and efficiently using a one-step method, making it a promising new radioactive tracer for PET imaging in cancer diagnostics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Automatic Production and Preliminary PET Imaging of a New Imaging Agent [18F]AlF-FAPT. Huang, J., Fu, L., Hu, K., et al.[2022]

In a study involving 19 patients with head and neck and gastrointestinal cancers, dual-tracer PET/CT using [18F]FDG and [68Ga]Ga-FAPI-46 provided better visualization of tumors, showing higher target-to-background ratios (TBRs) and larger functional tumor volumes (FTV) compared to single-tracer PET/CT.

The dual-tracer approach was superior in detecting malignant tissue in 6 out of 19 patients, indicating that [68Ga]Ga-FAPI-46 enhances the diagnostic performance and staging of cancer, making it a valuable tool in pretherapeutic assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual-tracer PET/CT protocol with [18F]FDG and [68Ga]Ga-FAPI-46 outperforms single-tracer PET/CT with [18F]FDG in different cancer types, resulting in larger functional and gross tumor volume. Wegen, S., Weindler, J., Voltin, CA., et al.[2023]

FAPI-04, a modified fibroblast activation protein inhibitor, shows excellent stability and higher affinity for cancer-associated fibroblasts compared to previous versions, making it a promising candidate for imaging and therapy in tumors like breast cancer.

In a proof-of-concept study with two patients, FAPI-04 demonstrated high uptake in metastatic lesions and resulted in pain reduction after treatment with a low dose of 90Y-FAPI-04, indicating its potential efficacy in targeted cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of Quinoline-Based Theranostic Ligands for the Targeting of Fibroblast Activation Protein. Lindner, T., Loktev, A., Altmann, A., et al.[2021]

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

The study involved 6 patients with invasive lobular breast cancer who underwent 24 scans, showing that the 68 Ga-FAPI PET/CT radiotracer effectively correlates tumor volume with blood biomarkers, indicating its potential for monitoring cancer progression and treatment response.

While 68 Ga-FAPI showed a strong correlation with blood biomarkers (r = 0.7, P < 0.01), it had a weaker correlation with traditional CT imaging, suggesting that FAPI may provide additional insights into tumor behavior that standard imaging might miss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of 68 Ga-FAPI PET/CT in Breast Cancer Response Assessment and Follow-Up. Eshet, Y., Tau, N., Levanon, K., et al.[2023]

In a study of 32 cancer patients undergoing Ga-68 FAPI PET scans, 18.8% showed increased myocardial uptake of the tracer, indicating potential cardiac involvement that may be linked to underlying coronary artery disease (CAD).

The study found significant correlations between myocardial FAPI uptake and factors such as age, coronary artery disease, and left ventricular ejection fraction, suggesting that FAPI imaging could help in assessing cardiac risk and monitoring heart health in cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac fibroblast activation detected by Ga-68 FAPI PET imaging as a potential novel biomarker of cardiac injury/remodeling. Siebermair, J., Köhler, MI., Kupusovic, J., et al.[2023]

In a study of 137 patients using 68Ga-FAPI-04 PET imaging, 392 non-tumoral regions were identified, showing that high uptake of this radiopharmaceutical can occur in various normal tissues, such as the submandibular gland and uterus.

The findings indicate that high uptake of 68Ga-FAPI-04 does not always indicate cancer, as many physiological and benign conditions can also show similar uptake patterns, highlighting the importance of understanding these variations for accurate diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-tumoral uptake of 68Ga-FAPI-04 PET: A retrospective study. Qi, N., Wang, H., Wang, H., et al.[2022]

68Ga-FAPI-04 is an effective PET imaging agent that can help diagnose conditions like IgG4-related disease (IgG4-RD) by targeting fibroblast activation protein, which is often present in tumors and inflammatory tissues.

In a case study of a 62-year-old patient, 68Ga-FAPI PET provided clearer diagnostic information than traditional 18F-FDG PET, highlighting its potential to differentiate between pancreatitis and pancreatic cancer when other imaging results are inconclusive.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

68Ga-FAPI-04 PET/MR is helpful in differential diagnosis of pancreatitis from pancreatic malignancy compared to 18F-FDG PET/CT: a case report. Shou, Y., Xue, Q., Yuan, J., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11043111/

Initial results with [18F]FAPI-74 PET/CT in idiopathic ... The initial results confirm our assumption that [18F]FAPI-74 offers a viable non-invasive assessment method for pulmonary fibrotic changes in patients with IPF.

2. nature.com nature.com/articles/s44303-024-00053-z

Clinical applications of fibroblast activation protein inhibitor ... F-FAPI-74 PET outperforms 18F-FDG PET in detecting primary tumors (patients 11, 39, 50, 58, 79, and 101; solid black arrows), local recurrences ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06413355

NCT06413355 | FAPI-74 PET/CT in Adults with Fibrosis A study to evaluate subjects with fibrosis-inducing medical conditions that are known or suspected to cause tissue fibrosis (e.g. cancer-associated, post- ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-06149

18F-Fibroblast Activation Protein Inhibitor ([18F]FAPI-74) ... Researchers believe that [18F]FAPI-74 PET imaging may be able to visualize cancer more effectively than the approved tracers. If so, the new tracer would make ...

5. pubs.acs.org pubs.acs.org/doi/pdf/10.1021/acs.bioconjchem.5c00366?ref=article_openPDF

Synthesis and Preclinical Evaluation of Druglike 18F‑ ... Compared to the clinically used. [18F]AlF-NOTA-FAPI-74, [18F]5a and [18F]5b, exhibited significantly improved tumor retention at 6 h p.i. ([18F] ...

6. sofie.com sofie.com/2025/10/01/sofie-biosciences-prepares-launch-of-two-18ffapi-74-phase-3-studies-following-successful-fda-engagement/

SOFIE Biosciences Prepares Launch of Two [18F]FAPI-74 ... This meeting comes after a favorable Phase 2, multicenter, non-randomized study of [18F] FAPI-74 in patients with gastrointestinal cancers, ...

7. clinicaltrials.gov clinicaltrials.gov/ct2/show/record/NCT06503146

18F-Fibroblast Activation Protein Inhibitor ([18F]FAPI-74) ... Also called a data safety and monitoring board, or DSMB. Early Phase 1 (formerly listed as Phase 0). A phase of research used to describe exploratory trials ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9232873/

Clinical summary of fibroblast activation protein inhibitor ... Herein, we present a comprehensive review of radiolabeled FAPI, including their clinical translation, in order to clarify the current and potential future role ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT06413355

NCT06413355 | FAPI-74 PET/CT in Adults with Fibrosis A study to evaluate subjects with fibrosis-inducing medical conditions that are known or suspected to cause tissue fibrosis (e.g. cancer-associated, post- ...