Integrin αvβ6‐Targeted PET/CT Imaging of Non‐Small Cell Lung Cancer with [ 68 Ga]Ga‐Trivehexin: Improved Preoperative Lymph Node Staging and Association with Immunohistochemistry

Integrin αvβ6, an epithelial-specific integrin, plays a crucial role in the development and prognosis of multiple tumors and has emerged as a potential target for cancer diagnosis and treatment. The novel integrin αvβ6-targeted radiotracer [⁶⁸Ga]Ga-Trivehexin shows excellent targeting specificity and favorable tumor-to-background contrast. In this prospective clinical study (NCT05835570) involving 58 participants with non-small cell lung cancer (NSCLC), [⁶⁸Ga]Ga-Trivehexin and 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) positron emission tomography/computed tomography (PET/CT) showed perfect diagnostic accuracy (100%, 58/58) for the detection of primary tumors. In detecting lymph node metastasis, [⁶⁸Ga]Ga-Trivehexin exhibited similar diagnostic sensitivity to [¹⁸F]FDG PET/CT (80.0% vs 72.0%), with higher specificity (93.8% vs 62.5%, p < 0.001) and accuracy (91.2% vs 64.2%, p < 0.001) in per-station analysis. [⁶⁸Ga]Ga-Trivehexin outperformed [¹⁸F]FDG in detecting brain metastasis (sensitivity, 92.3% vs 38.5%; p = 0.031). Additionally, [⁶⁸Ga]Ga-Trivehexin PET/CT results changed the therapeutic regimens of 14 (24.1%) participants. The maximum standardized uptake value (SUVmax) and tumor-to-liver parenchyma ratio (TLR) derived from [⁶⁸Ga]Ga-Trivehexin correlated with integrin β6 expression in NSCLC. Overall, [⁶⁸Ga]Ga-Trivehexin PET/CT represents an invaluable tool for identifying lymph node and brain metastases and shows comparable diagnostic efficacy in detecting primary tumors and other distant metastases compared with [¹⁸F]FDG in NSCLC, potentially guiding treatment decision-making.