Clinical Study of Trap-(FAPI)3 PET Imaging in the Diagnosis of Pulmonary Nodules

The excellent tumor-targeting efficacy of FAP has been confirmed by multiple clinical studies. The results unequivocally establish FAPI as a tumor-targeting ligand with significant potential, demonstrating important application prospects in translational oncology. However, its therapeutic effects remain under investigation. An ideal radiopharmaceutical for cancer treatment should possess outstanding targeting specificity and relatively prolonged tumor retention time. Previous studies have shown that radiolabeled FAPI variants (FAPI-04 and FAPI-46) rapidly and satisfactorily accumulate in tumors, while exhibiting low physiological uptake in normal tissues. However, prior FAP-related tracers demonstrated relatively short retention times in small pulmonary lesions. Our aim is to design a FAPI trimer, Trap-(FAPI)3, to optimize pharmacokinetics and evaluate whether this novel drug offers superior advantages over its monomer analogs in the imaging diagnosis and staging of pulmonary tumors.

Study Overview

• Status: Not yet recruiting
• Conditions: Lung Nodules

Detailed Description

Positron Emission Tomography (PET) is a functional imaging technology for the diagnosis and monitoring of tumors. The clinical applications of PET in malignant tumors, including staging, response evaluation, and efficacy prediction, provide attractive semi-quantitative biomarkers for clinical and research platforms. Understanding the advantages and limitations of fundamental imaging science and imaging modalities is crucial for optimizing research evaluations. With the widespread use of functional techniques and the development of novel PET biomarkers, PET research evaluations will be further improved.

The field of oncology has undergone a revolution due to molecular imaging, which evaluates tumor biology, while traditional radiological imaging focuses on morphological anatomy. Molecular imaging employs non-invasive visualization of physiological or pathological processes at the cellular or subcellular level. Positron Emission Tomography/Computed Tomography (PET/CT) is a hybrid imaging tool that provides complementary information on both function and structure. [18F]Fluorodeoxyglucose (FDG), first developed in the late 1970s as a tracer for brain metabolism, is now the most widely used PET tracer with applications in both oncological and non-oncological pathways. Although its clinical utility is undeniable, FDG uptake serves as a surrogate indicator for glucose transport/metabolism and is not specific to malignant tumors. The diagnostic accuracy of FDG for pulmonary nodules has long been a challenge, as tumor cells are scarce, solid components are minimal, and mucinous components are excessive. Multiple factors can lead to low uptake or no uptake of pulmonary nodules.

Through continuous exploration of cellular targets, fibroblast-activating protein (FAP) was identified. Cancer-associated fibroblasts are present in numerous tumors, particularly those with strong fibroblast proliferation responses, such as breast cancer, colorectal cancer, pancreatic cancer, prostate cancer, and lung cancer. Consequently, FAP expression is detected in over 90% of epithelial tumors. To date, FAP expression has been reported to correlate with poor tumor prognosis, as observed in colorectal cancer, pancreatic cancer, hepatocellular carcinoma, and ovarian cancer. Although further research is required, this advantage positions cancer-associated fibroblasts as an ideal target for antitumor therapy. In practical applications, low FAP expression in fibroblasts or healthy tissues facilitates imaging of pathological changes with low background signals.

Cancer-associated fibroblasts (CAFs) are key components of the tumor microenvironment, accounting for over half of the mass in various types of tumors. Previous studies have demonstrated that CAFs play significant roles in tumor growth, immunosuppression, and cancer invasion. Consequently, CAFs may emerge as a novel therapeutic target for lung tumor diagnosis and treatment. Fibroblast-activating protein (FAP) is overexpressed in CAFs of multiple epithelial cancers but weakly expressed in healthy tissues, making it an attractive target in cancer research. In recent years, molecular imaging targeting FAP has been extensively explored in the field of tumor diagnosis.

The excellent tumor-targeting efficacy of FAP has been confirmed by multiple clinical studies. The results unequivocally establish FAPI as a tumor-targeting ligand with significant potential, demonstrating important application prospects in translational oncology. However, its therapeutic effects remain under investigation. An ideal radiopharmaceutical for cancer treatment should possess outstanding targeting specificity and relatively prolonged tumor retention time. Previous studies have shown that radiolabeled FAPI variants (FAPI-04 and FAPI-46) rapidly and satisfactorily accumulate in tumors, while exhibiting low physiological uptake in normal tissues. However, prior FAP-related tracers demonstrated relatively short retention times in small pulmonary lesions. Our aim is to design a FAPI trimer, Trap-(FAPI)3, to optimize pharmacokinetics and evaluate whether this novel drug offers superior advantages over its monomer analogs in the imaging diagnosis and staging of pulmonary tumors.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

Study Locations

• China
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China, 400010
      • Department of Nuclear Medicine, Daping Hospital of Army Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

The subjects we selected are adults who are not restricted by gender. Fordetails, please refer to the "EligibilityCriteria" colymn.

Description

Inclusion Criteria:

• 1) Patients aged over 18 years with no gender restriction;
• 2) Patients with radiographic findings of pulmonary nodules;
• 3) Patients eligible for Trap-(FAPI)3 PET examination;
• 4) Written informed consent signed by the subject or their legal guardian.

Exclusion Criteria:

• 1) Patients who have received antitumor therapy prior to PET/CT scanning;
• 2) Patients with severe diseases that cannot tolerate PET/CT scanning;
• 3) Alternative subjects with contraindications to PET/CT scanning;
• 4) Radiation exposure exceeding 50 mSv dose in the past year;
• 5) Alternative subjects who underwent major surgery within the past 3 months; those who received experimental drugs or devices (with unclear efficacy or safety) within the past 1 month;
• 6) Alternative subjects with any clinical conditions that the principal investigator of this study considers may cause or pose potential hazards from the investigational product.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
patients with pulmonary nodules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metabolic parameters	Total Lesion Glycolysis (TLG) of bowel lesions are measured on PET.	Completed within one week after PET examination
Diagnostic efficacy of Trap-(FAPI)3 probe for pulmonary nodules	sensitivity, specificity, accuracy, positive and negative predictive values, ROC curve analysis,	through study completion, an average of 1 year
Histologic Scores for Fibrotic	Paraffin section specimens were stained by using Masson trichrome for the histologic fibrosis score. Two pathologists graded the histologic slices from the most severe areas for fibrosis by using a semiquantitative scoring system. The fibrosis score was scored between 0 and 3 points as follows: 0: none (No fibrosis), 1: mild (Minimal fibrosis in submucosa or subserosa), 2: moderate (Increased submucosal fibrosis, septa into muscularis propria and/or septa through muscularis propria, increase in subserosal collage), 3: severe (Significant transmural scar, marked subserosal collagen).	Completed within one week after surgery

Collaborators and Investigators

• Sponsor: Daping Hospital and the Research Institute of Surgery of the Third Military Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: February 23, 2026
• First Submitted That Met QC Criteria: March 2, 2026
• First Posted (Actual): March 4, 2026

Study Record Updates

• Last Update Posted (Actual): March 4, 2026
• Last Update Submitted That Met QC Criteria: March 2, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: 2026033

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