c-MET is a receptor tyrosine kinase overexpressed in multiple malignancies and associated with tumor progression, therapeutic resistance, and poor prognosis, while showing limited expression in normal tissues, making it an attractive imaging and therapeutic target. Current assessment relies on invasive biopsy and is limited by tumor heterogeneity and sampling bias.

FL-261 is a novel c-MET-targeting ligand with high affinity and specificity, favorable tumor uptake and retention, rapid background clearance, and good preclinical safety. It can be radiolabeled for both diagnostic imaging and potential theranostic applications.

This first-in-human study will evaluate [68Ga]Ga-FL-261 PET or [111In]In-FL-261 SPECT imaging in patients with advanced malignancies, including non-small cell lung cancer, colorectal cancer, and head and neck cancer. The study aims to assess safety, biodistribution, and tumor-targeting capability, and to explore its diagnostic value by correlating imaging findings with histopathological c-MET expression.

Inclusion Criteria:

• Ability to provide written informed consent (by the subject or legally authorized representative)
• Willingness and ability to comply with all study procedures
• Age ≥18 years, any sex
• Clinically suspected or histologically confirmed malignancies (e.g., non-small cell lung cancer, colorectal cancer, head and neck cancer), supported by tumor markers, imaging (ultrasound, CT, MRI), or pathology
• Good general condition
• Agreement to use existing tissue samples

Exclusion Criteria:

• Inability or unwillingness to provide informed consent
• Inability to comply with study procedures
• Acute systemic disease or significant electrolyte imbalance
• Pregnant or breastfeeding women
• Any condition deemed unsuitable by the investigator (e.g., known intolerance to c-MET-targeted agents)

Patients with clinically suspected or histologically confirmed malignancies, including non-small cell lung cancer, colorectal cancer, and head and neck cancer, will undergo [68Ga]Ga-FL-261 PET or [111In]In-FL-261 SPECT imaging, with optional [18F]FDG PET for comparison. This study is a single-arm diagnostic study without a control group.