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Abstract #4255

Allysine-targeting gadolinium-based MRI probes for imaging lung fibrogenesis

Eman Akam1, Nicholas Rotile1, Iris Y Zhou1, Eric Abston2, and Peter Caravan1

1Radiology, A. A. Martinos Center for Biomedical Imaging and the Institute for Innovation in Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States, 2Department of Medicine: Pulmonary, Allergy, Sleep and Critical Care Medicine, Boston University School of Medicine, Boston, MA, United States

There is an enormous unmet medical need for non-invasive methods to assess lung fibrosis that can distinguish between active disease and stable scar. Here, we report on a gadolinium-containing contrast agent Gd-CHyd that targets fibrogenesis (active fibrosis) by undergoing a condensation reaction with allysine, an abundant aldehyde motif on fibrosing tissue. This probe reacts with aldehydes at a rate that is an order of magnitude faster than the parent probe Gd-Hyd. This faster reactivity leads to higher accumulation of the probe in the lungs of bleomycin treated mice (mouse model of lung fibrosis) and two-fold contrast enhancement relative to Gd-Hyd.

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