Interstitial and Diffuse Lung Disease NetWork
Advances in molecular imaging in pulmonary fibrosis
Fibrotic interstitial lung diseases (ILD), including idiopathic pulmonary fibrosis (IPF), have poor prognosis with marked heterogeneity in the clinical course. Treatment options, including antfibrotic drugs and immunosuppressants, are fairly limited for either conditions, and there is wide variability in drug responsiveness. Biomarkers that predict disease course and enable patient stratification to assess responsiveness to specific therapies play a crucial role in management of this fatal disease.
Dr. Tejaswini Kulkarni
Molecular imaging has the ability to noninvasively provide both structural details, as well as functional/molecular information at the cellular level; it has thus developed into a powerful tool for several inflammatory and malignant disease processes. Probes that specifically target fibrosis-specific pathways utilizing positron emission tomography (PET) or magnetic resonance (MR) imaging have gained traction recently.
The most commonly used radiopharmaceutical for PET, 18F-FDG, is significantly increased in areas of established fibrosis in patients with IPF and autoimmune ILDs (Win, et al. Eur J Nucl Med Mol Imaging. 2018 May;45[5]:806; Uehara, et al. Mod Rheumatol. 2016;26[1]:121-7), as well as areas with seemingly normal morphologic appearance on HRCT scan (Win, et al. Eur J Nucl Med Mol Imaging. 2014 Feb;41[2]:337). While this probe was shown to have some potential for prognostication, there has been concern regarding the specificity of FDG uptake in fibrotic lung diseases. Hence, other probes that target specific fibrosis-related cellular mechanisms such as macrophages (Withana, et al. Nature Scientific Reports. 2016;6 [Jan 22):19755], and John, et al. J Nucl Med. 2013;54[12]:2146) and matrix proteins (Montesi, et al. Am J Respir Crit Care Med. 2019 Jul 15;200[2]:258) have been developed in preclinical fibrosis/lung injury models and are being translated to human subjects.
With the ability to capture early fibrogenesis and target engagement, molecular imaging has the potential to prognosticate patients, provide earlier evaluation of treatment responsiveness and have a promising application in clinical trial design for fibrotic lung diseases.
Tejaswini Kulkarni, MD
Steering Committee Member