[⁶⁸Ga]Ga-Trivehexin PET/CT imaging of integrin-αvβ6 expression in concomitant mucinous lung adenocarcinoma and idiopathic pulmonary fibrosis

A 54-year-old man came to hospital due to a dry cough for over two months. Chest CT showed an irregular soft tissue mass measuring 52 × 23 × 20 mm in the superior lobe of the left lung, suggesting the possibility of malignancy (c). In addition, diffuse ground glass opacities with reticular thickening were observed in the subpleural regions, indicating interstitial lung disease (d-e). To further determine the preoperative staging, the patient participated in a paired clinical trial (NCT05835570) and signed an informed consent form. [⁶⁸Ga]Ga-Trivehexin PET/CT showed high tracer uptake in the mass (SUVmax, 5.03; a and f), which was higher than that of [¹⁸F]FDG (SUVmax, 3.76; b and i). More surprisingly, interstitial lung disease also exhibited remarkable uptake with an SUVmax of 5.53 on [⁶⁸Ga]Ga-Trivehexin (a, g, and h; red arrows), whereas negative uptake was observed on [¹⁸F]FDG PET (b, j, and k). Surgical pathology confirmed mucinous adenocarcinoma and peritumoral fibrosis (l, n), and immunohistochemical staining showed β6 expression not only in tumor cells (m, blue arrows) but also in alveolar epithelium within areas of fibrosis (m, red arrows). The patient was eventually diagnosed with idiopathic pulmonary fibrosis (IPF) and received postoperative treatment with nintedanib. Integrin-αvβ6, known as “cancer integrin”, has also emerged as a potential biomarker for both targeted diagnosis and therapy in IPF [1‐5]. Our case highlights that [⁶⁸Ga]Ga-Trivehexin, a novel trimeric probe based on a cyclic nonapeptide, is a promising tracer for detecting lung cancer and IPF, potentially guiding risk stratification, treatment decision-making and evaluation of therapeutic effect [6‐9]. …