PET-MR Imaging of pulmonary fibrosis

Project Summary/Abstract
The goal of this project is to use quantitative PET-MR imaging of the lung to accurately quantify molecular
abnormalities associated with pulmonary fibrosis, to predict disease progression, and to provide an early
indication of whether anti-fibrotic therapy is likely to be effective. Idiopathic pulmonary fibrosis (IPF) is a
progressive and ultimately fatal disease with a median survival of less than 4 years from the time of diagnosis.
The treatment options remain limited due to highly variable clinical course and poorly understood pathogenic
mechanisms. Current strategies to diagnose and monitor IPF include lung biopsy, pulmonary function tests that
measure global lung function, and anatomic imaging tools such as high-resolution computed tomography
(HRCT). Yet these methods are limited in their ability to detect disease early, determine disease activity at any
one measure, or monitor the therapeutic response. Molecular imaging may be an alternative approach that is
more sensitive to detect early fibrosis and potentially capable of distinguishing new, active fibrosis from stable
disease – urgent and unmet clinical needs. Our group recently developed a type I collagen-specific positron
emission tomography (PET) probe, 68Ga-CBP8, which was shown in animal models to detect pulmonary fibrosis
at an early stage and was capable of monitoring treatment response. Preliminary data with this probe in healthy
volunteers and IPF patients demonstrated that 68Ga-CBP8 had significantly higher uptake in IPF lungs than in
normal lungs. This data also showed that in addition to probe uptake in regions of lung with fibrosis as
established by HRCT, there were additional areas of probe uptake in radiographically “normal” lung suggesting
that the probe may be sensitive to lower levels of fibrosis than HRCT and/or sensitive to disease activity, i.e.
newly formed collagen. Magnetic resonance imaging (MRI) on the other hand can provide multiple readouts of
morphology, physiology, and function. Preliminary data from our lab using dynamic contrast enhanced-MRI
(DCE-MRI) in healthy controls and IPF subjects indicated that DCE parameters can distinguish abnormal from
normal lung, and that these measures may predict disease progression. Quantitative MRI-PET in lung has been
historically limited because of low proton density and the fast signal decay due to susceptibility artefacts at air-
tissue interfaces for MRI, while PET quantification remains challenging due to respiratory motion, photon
attenuation and regional variations in tissue, air and blood fractions. However, combining the two modalities
holds great potential to overcome some of these limitations. Our central hypothesis is that non-invasive molecular
imaging of collagen accumulation will allow us to capture the extent of ongoing lung injury in IPF patients and
that a bi-modal imaging approach using collagen-targeted PET augmented by DCE-MRI will enable more
accurate detection of disease activity and treatment response.

Grant Number: 5R01HL153606-05
NIH Institute/Center: NIH
Principal Investigator: Peter Caravan