Translocator protein targeted molecular imaging in idiopathic pulmonary fibrosis

Abstract

Targeted molecular imaging utilizing positron emission tomography (PET) technology may provide a non-invasive biomarker in idiopathic pulmonary fibrosis (IPF). Translocator protein (TSPO, 18 kDa), a mitochondrial outer membrane protein, is upregulated in persistent injury and inflammation. Hence, we evaluated the TSPO-targeting PET tracer [ 18 F]DPA-714, to detect disease activity in IPF. In this prospective study, 7 participants with IPF and 3 healthy controls (HCs) were enrolled, all confirmed as either mixed- (MAB) or high-affinity binders (HAB) based on genotyping for SNP rs6971 polymorphism in the TSPO gene. Imaging was performed on a GE 710 PET/CT scanner with respiratory gating 30–60 min after IV administration of [ 18 F]DPA-714. Regions of interest were defined using non-contrast CT. Mean and maximum standardized uptake values (SUVmean, SUVmax) were measured in whole lung, mediastinal, and axillary lymph nodes (all participants), and fibrotic lesions (IPF only). Participants with IPF had a median age of 74 years; 71% were male. HCs had a median age of 47 years. Five participants were HABs(3 IPF,2 HCs) and five were MABs(4 IPF,1 HC). In IPF, mediastinal lymph node SUVmax was significantly higher than axillary lymph nodes [median 5.3,(4.5,6.8) vs 2.1,(1.8,2.4), p = 0.02], and fibrotic lesions demonstrated 2.5-fold higher SUVmean than normal lung [median 4.1(3.9,5.1) vs 1.6(1.2,2.2), p = 0.02]. Mediastinal lymph node uptake was numerically higher in IPF than HCs within affinity groups, while total lung SUVmean varied. TSPO imaging with [ 18 F]DPA-714 PET is safe and feasible in IPF. This study supports further prospective evaluation of the probe as a marker of disease activity and its relationship with longitudinal disease progression and clinical outcomes in a larger cohort. Clinicaltrials.gov (NCT04362644), Date of registration: 4/23/2020.