Assessment of Pulmonary Fibrosis and Pleural Invasion in Lung Cancer with Elastin-Targeting Molecular Imaging.

Elastin plays crucial structural roles in maintaining lung architecture and function while actively participating in disease pathogenesis, particularly in pulmonary fibrosis (PF) and lung cancer. Pathological alteration in the elastin architecture is a key histopathological hallmark of disease progression and presents a promising target for diagnosis. In this study, we developed a class of elastin-targeting molecular imaging probes with a modular design that enables flexible incorporation of wavelength-tunable fluorophores via streamlined one-step conjugation chemistry. Using bleomycin-induced preclinical PF models, we demonstrated both in vitro and in vivo the feasibility of this elastin imaging approach for disease detection, staging, and post-treatment monitoring. The imaging approach was further extended to human nonsmall cell lung cancer samples, where the probes enabled visualization of the fibrotic tumor microenvironment and facilitated the detection of visceral pleural invasion, a critical determinant in lung cancer staging. These findings highlight the potential of the elastin-targeting imaging probes as a specific and versatile tool for noninvasive assessment of pathological conditions involving elastin dysregulation.