Integrin αvβ6‐Targeted PET/CT Imaging of Non‐Small Cell Lung Cancer with 68GaGa‐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 68GaGa-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), 68GaGa-Trivehexin and 2-deoxy-2-18Ffluoro-D-glucose (18FFDG) 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, 68GaGa-Trivehexin exhibited similar diagnostic sensitivity to 18FFDG 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. 68GaGa-Trivehexin outperformed 18FFDG in detecting brain metastasis (sensitivity, 92.3% vs 38.5%; p = 0.031). Additionally, 68GaGa-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 68GaGa-Trivehexin correlated with integrin β6 expression in NSCLC. Overall, 68GaGa-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 18FFDG in NSCLC, potentially guiding treatment decision-making.