Exploring the Application Value of PET Molecular Imaging Targeting FAP in Oral Squamous Cell Carcinoma (FAPI-OSCC)

In this prospective study, the investigators will use integrated PET/CT with the agent 68Ga-FAPI and conventional imaging agent 18F-FDG to explore the application value of FAP-targeted molecular imaging in the diagnosis and staging for oral cancer. This study also aims to explore the application value of FAPI imaging in evaluating treatment response for oral cancer.

Study Overview

• Status: Recruiting
• Conditions: Oral Cancer; PET/CT; FAPI
• Intervention / Treatment: Drug: 68Ga-DOTA-FAPI; Device: PET/CT; Diagnostic test: Participants receive baseline paired FDG and FAPI PET/CT. For resectable locally advanced cases receiving neoadjuvant therapy undergo follow-up FAPI PET imaging.

Detailed Description

Positron emission tomography (PET) molecular imaging provides a valuable method for the diagnosis, differential diagnosis and staging of various tumors. Cancer associated fibroblasts (CAFs) are the main components of tumor stroma, which are involved in tumor cell proliferation, invasion, metastasis and tumor angiogenesis, and play an important role in the occurrence and development of tumors. Fibroblast activation protein (FAP) is the most potential specific molecular marker of CAF, which is mainly expressed in stromal fibroblasts of epithelial tumors and is a potential molecular target for tumor diagnosis and treatment. Oral cancer is the most common type of malignant head and neck cancer, seriously endangering human health. Accurate delineation of the primary tumor, detection of regional nodal metastases, distant metastases and second primary tumors are important for determining the therapeutic strategy and prognosis of oral cancer. Currently, the molecular imaging agent most commonly used in clinical practice for oral cancer is 18F-fluoro-deoxy-glucose (18F-FDG). However, 18F-FDG exhibits some shortages. Inflammatory lesions and the surrounding normal tissue such as brain, tonsils and salivary glands show high uptake of 18F-FDG, often affecting the judgment of lesions.

Adult patients aged >18 years with clinically confirmed or highly suspected oral cancer will be enrolled. Participants receive paired baseline FDG and FAPI PET/CT to explore the diagnostic and staging value of FAPI PET in oral cancer. For resectable locally advanced cases receiving neoadjuvant therapy from oral and maxillofacial clinicians, a follow-up FAPI PET imaging will be performed after two cycles of treatment and before surgery to evaluate its application in treatment-response assessment. Ultimately, this study aims to comprehensively evaluate the clinical utility of FAPI PET/CT in oral cancer.

• Study Type: Observational
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jiang Yaqun, PhD; Phone Number: 0086-027-67812698; Email: zn004239@whu.edu.cn
• Study Contact Backup: Name: He Yong, PhD; Phone Number: 0086-027-67812698; Email: vincentheyong@163.com

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430071
      • Recruiting
      • Zhongnan Hopital of Wuhan University
      • Contact: Yaqun Jiang, PhD, MD; Phone Number: 027-67812837; Email: zn004239@whu.edu.cn
      • Contact: Yong He, PhD, MD; Phone Number: 027-67812837; Email: vincentheyong@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This study enrolls adults aged 18-70 years with clinically suspected or histopathologically confirmed oral cancer (primary or recurrent). Newly diagnosed patients are scheduled for surgery or neoadjuvant therapy, while recurrent cases require imaging/pathology confirmation. All participants must complete baseline FAPI PET/CT and FDG PET/CT for diagnostic/staging evaluation. Locally advanced patients receiving neoadjuvant therapy will undergo follow-up FAPI PET/CT for therapeutic response assessment. Exclusion criteria include pregnancy, severe allergies to FAPI/FDG, uncontrolled comorbidities, and recent participation in other interventional trials.

Description

Inclusion Criteria:

1. Voluntary participation with signed informed consent;
2. Aged 18~70 years;
3. Clinically highly suspected oral cancer and recurrence after treatment (Newly diagnosed patients: Scheduled for surgery or neoadjuvant therapy followed by surgery);
4. Ability to complete baseline and follow-up PET/CT (Follow-up FAPI PET/CT applies only to locally advanced patients undergoing neoadjuvant therapy.).

Exclusion Criteria:

1. Pregnant or breastfeeding women, or women planning pregnancy during the trial period;
2. Known hypersensitivity to FAPI, FDG, or their components, or history of severe allergic reactions;
3. People with poor general condition, their heart, lung, liver, kidney and other important organ functions cannot tolerate surgery;
4. Before the injection of 18F-FDG, the fasting blood glucose level exceeded 11.0 mmol/L;
5. Claustrophobia or inability to tolerate PET/CT imaging (Those who cannot tolerate lying supine for 15~30 minutes.);
6. Participation in another interventional clinical trial within 30 days prior to enrollment, or planned participation during this study.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

68Ga-DOTA-FAPI and 18F-FDG PET/CT; Investigators recruit patients whom are clinically highly suspected oral cancer or recurrence after treatment. Patients undergo baseline 68Ga-FAPI and 18F-FDG PET/CTwithin one week. For resectable locally advanced cases receiving neoadjuvant therapy from oral and maxillofacial clinicians, a follow-up FAPI PET imaging will be performed after two cycles of treatment and before surgery.

Drug: 68Ga-DOTA-FAPI; Intravenous access is pre-established. Quality control is carried out to confirm the radiochemical purity of 68Ga-DOTA-FAPI by HPLC. Intravenous administration of 68Ga-DOTA-FAPI according to 1.85-3.7 MBq/kg body weight (0.05-0.1 mCi/kg), rinsed with 0.9% saline, and hydrated after drinking more water.; Other Names: gallium-68 (68Ga)-Fibroblast activation protein inhibitor (FAPI); Device: PET/CT; Each subject undergoes PET/CT imaging within 20-30 minutes after injection.; Other Names: Positron Emission Tomography/Computed Tomography; Diagnostic test: Participants receive baseline paired FDG and FAPI PET/CT. For resectable locally advanced cases receiving neoadjuvant therapy undergo follow-up FAPI PET imaging.; This observational study evaluates the application of paired FDG and FAPI PET/CT in oral cancer.; Baseline phase: All participants undergo baseline FDG and FAPI PET/CT scans.; Post-neoadjuvant phase: For patients with resectable locally advanced disease receiving neoadjuvant therapy (as per clinician decision), a second FAPI PET/CT scan is performed after 2 cycles of treatment to assess treatment response.; Purpose: To explore the utility of FAPI PET in (a) initial staging, (b) treatment response evaluation, and (c) prognostic value in oral cancer.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic performance (sensitivity, specificity, accuracy) and staging of FAPI PET in oral cancer	Comparison of FAPI PET and FDG PET in diagnosing oral cancer, including sensitivity, specificity, accuracy, and TNM staging. Assessments performed at baseline using histopathology and imaging as reference standards.	Baseline (at initial diagnosis, prior to treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FAPI PET for therapeutic response evaluation	Assessment of FAPI PET parameters for predicting treatment response in patients receiving neoadjuvant therapy. Follow-up FAPI PET performed post-treatment.	After completion of 2nd cycle of neoadjuvant therapy, just prior to surgery
Prognostic value of FAPI PET parameters in oral cancer	Correlation between FAPI PET parameters and long-term outcomes (e.g., progression-free survival, overall survival).	Through study completion, an average of 1 year
Correlation between FAPI PET parameters and histopathological biomarkers	Correlation between FAPI PET parameters (SUVmax/SUVmean/SUVpeak) and histopathological biomarkers of tumor tissue.; FAP expression level (H-score; immunohistochemistry); PD-L1 expression (Combined Positive Score; Dako 22C3 IHC assay); CD8 expression (H-score; immunohistochemistry); Granzyme B expression (H-score; immunohistochemistry)	At baseline and 6 weeks post-FAPI PET scan

Collaborators and Investigators

• Sponsor: Zhongnan Hospital
• Investigators: Study Chair: He Yong, PhD, Zhongnan Hospital

Publications and helpful links

General Publications

• Fitzgerald AA, Weiner LM. The role of fibroblast activation protein in health and malignancy. Cancer Metastasis Rev. 2020 Sep;39(3):783-803. doi: 10.1007/s10555-020-09909-3.
• Syed M, Flechsig P, Liermann J, Windisch P, Staudinger F, Akbaba S, Koerber SA, Freudlsperger C, Plinkert PK, Debus J, Giesel F, Haberkorn U, Adeberg S. Fibroblast activation protein inhibitor (FAPI) PET for diagnostics and advanced targeted radiotherapy in head and neck cancers. Eur J Nucl Med Mol Imaging. 2020 Nov;47(12):2836-2845. doi: 10.1007/s00259-020-04859-y. Epub 2020 May 23.
• Chen H, Pang Y, Wu J, Zhao L, Hao B, Wu J, Wei J, Wu S, Zhao L, Luo Z, Lin X, Xie C, Sun L, Lin Q, Wu H. Comparison of [68Ga]Ga-DOTA-FAPI-04 and [18F] FDG PET/CT for the diagnosis of primary and metastatic lesions in patients with various types of cancer. Eur J Nucl Med Mol Imaging. 2020 Jul;47(8):1820-1832. doi: 10.1007/s00259-020-04769-z. Epub 2020 Mar 28.

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2021
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: August 26, 2021
• First Submitted That Met QC Criteria: August 26, 2021
• First Posted (Actual): September 1, 2021

Study Record Updates

• Last Update Posted (Actual): May 28, 2025
• Last Update Submitted That Met QC Criteria: May 21, 2025
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mouth Diseases; Stomatognathic Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Neoplasms, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Squamous Cell; Mouth Neoplasms
• Other Study ID Numbers: PTXM2021021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No