Noninvasive Quantification of Radiation-Induced Lung Injury Using a Targeted Molecular Imaging Probe.

Abstract

Radiation-induced lung injury (RILI) is a progressive inflammatory process seen after irradiation for lung cancer. The disease can be insidious, often characterized by acute pneumonitis followed by chronic fibrosis with significant associated morbidity. No therapies are approved for RILI, and accurate disease quantification is a major barrier to improved management. Here, we sought to noninvasively quantify RILI using a molecular imaging probe that specifically targets type 1 collagen in mouse models and patients with confirmed RILI. Using a murine model of lung radiation, mice were imaged with EP-3533, a type 1 collagen probe, to characterize the development of RILI and to assess disease mitigation after losartan treatment. The human analog probe ⁶⁸Ga-CBP8, targeting type 1 collagen, was tested on excised human lung tissue containing RILI and was quantified via autoradiography. ⁶⁸Ga-CBP8 positron emission tomography was used to assess RILI in vivo in 6 human subjects. Murine models demonstrated that probe signal correlated with progressive RILI severity over 6 months. The probe was sensitive to mitigation of RILI by losartan. Excised human lung tissue with RILI had increased binding versus unirradiated control tissue, and ⁶⁸Ga-CBP8 uptake correlated with collagen proportional area. Human imaging revealed significant ⁶⁸Ga-CBP8 uptake in areas of RILI and minimal background uptake. These findings support the ability of a molecular imaging probe targeted at type 1 collagen to detect RILI in preclinical models and human disease, suggesting a role for targeted molecular imaging of collagen in the assessment of RILI.