Fluorescent imaging agents for αVβ6 integrin-mediated detection 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 receptor has emerged as a biomarker for targeted diagnostics and therapeutics. In addition to targeted therapies, precision medicine relies on imaging agents to detect diseased regions and pathological processes, supporting early diagnosis, patient stratification, and evaluation of therapeutic response. Building on our expertise in the field of RGD-binding integrin cyclopeptides, the fluorescent conjugates 1-4 were synthesized 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). Following intranasal administration, these imaging agents were evaluated in a bleomycin-induced murine model of pulmonary fibrosis. Ex vivo biodistribution studies, performed by IVIS imaging and MALDI analysis, demonstrated a significant enhancement of fluorescence signal in fibrotic lungs. The selectivity of compounds 1-4 for integrin αVβ6, along with their preferential accumulation in diseased tissue, underscores their promise for improving both early detection and longitudinal monitoring of pulmonary fibrosis.