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In Vivo PET Imaging of Monocytes Labeled with [89Zr]Zr-PLGA-NH2 Nanoparticles in Tumor and Staphylococcus aureus Infection Models

by Massis Krekorian, Kimberley R. G. Cortenbach ,Milou Boswinkel, Annemarie Kip, Gerben M. Franssen, Andor Veltien, Tom W. J. Scheenen, René Raavé, Nicolaas Koen van Riessen, Mangala Srinivas, Ingrid Jolanda M. de Vries, Carl G. Figdor, Erik H. J. G. Aarntzen and Sandra Heskamp

Cancers 2021, 13(20), 5069. doi: 10.3390/cancers13205069


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.