Fluorescent Tracers for αVβ6 Integrin-mediated Imaging of Pulmonary Fibrosis

The integrin αVβ6 is nearly undetectable in healthy adult tissues but is upregulated in pathological conditions such as tumours and idiopathic pulmonary fibrosis (IPF). Owing to its disease specific expression, this integrin has emerged as a biomarker for targeted diagnostics and therapeutics. In fact, in addition to targeted drugs the precision medicine needs probes to visualize the diseased regions or the pathological processes with the aim to get an early diagnosis, to stratify the patients for the therapy, and to monitor therapeutic response. Building on our expertise in the field of RGD-binding integrin cyclopeptides, the fluorescent conjugates 1-4 were synthesized (Figure 1) to selectively visualize the fibrotic regions of the lungs overexpressing integrin αVβ6. These compounds are formed by αVβ6-targeting cyclopeptides linked to the fluorescent moieties ZW800-1 (compounds 1-2) or sulfo-cyanine5 (compounds 3-4). These tracers were evaluated in vivo in a bleomycin-induced murine model of pulmonary fibrosis, showing a significant increase in fluorescence intensity in fibrotic lungs. The selectivity of compounds 1-4 for integrin αVβ6, and their ability to concentrate in diseased tissue overexpressing this integrin highlight their potential to improve both pre- and post-diagnostic workflows.