Longitudinal Imaging Using PET/CT with Collagen-I PET-Tracer and MRI for Assessment of Fibrotic and Inflammatory Lesions in a Rat Lung Injury Model

Abstract

Non-invasive imaging biomarkers (IBs) are warranted to enable improved diagnostics and follow-up monitoring of interstitial lung disease (ILD) including drug-induced ILD (DIILD). Of special interest are IB, which can characterize and differentiate acute inflammation from fibrosis. The aim of the present study was to evaluate a PET-tracer specific for Collagen-I, combined with multi-echo MRI, in a rat model of DIILD. Rats were challenged intratracheally with bleomycin, and subsequently followed by MRI and PET/CT for four weeks. PET imaging demonstrated a significantly increased uptake of the collagen tracer in the lungs of challenged rats compared to controls. This was confirmed by MRI characterization of the lesions as edema or fibrotic tissue. The uptake of tracer did not show complete spatial overlap with the lesions identified by MRI. Instead, the tracer signal appeared at the borderline between lesion and healthy tissue. Histological tissue staining, fibrosis scoring, lysyl oxidase activity measurements, and gene expression markers all confirmed establishing fibrosis over time. In conclusion, the novel PET tracer for Collagen-I combined with multi-echo MRI, were successfully able to monitor fibrotic changes in bleomycin-induced lung injury. The translational approach of using non-invasive imaging techniques show potential also from a clinical perspective.

Imaging Biomarkers in Animal Models of Drug-Induced Lung Injury: A Systematic Review

“…Similar uptake of 68 Ga-CBP8 was found by ex vivo analysis of lung tissue from patients with IPF [ 34 ]. Most recently, this Collagen-I binding peptide was also evaluated in a rat model, using the radionuclide 64 Cu coupled to the small peptide CBP, for detection of newly synthesized Collagen-I in lung injury [ 36 ]. Among the PET studies, radiolabeled water (H 2 O 15 ) or oxygen ( 15 O) were also used for lung monitoring (14%).…”

The interplay of collagen, macrophages, and microcalcification in atherosclerotic plaque cap rupture mechanics

“…Recent hybrid imaging systems, such as PET–CT or PET–MRI can facilitate the detection of microcalcification and inflammation, to be able to create patient-specific modeling approaches and evaluate local mechanical properties [ 233 ]. Furthermore, specific tracers or diffusion tensor imaging can be used to visualize cap components, such as collagen type, maturity [ 192 ], and alignment [ 8 , 239 , 240 ].…”