LATE-BREAKING ABSTRACT: Molecular imaging with CXCR4-gallium-68-pentixafor PET correlates with GAP index and treatment effects in idiopathic pulmonary fibrosis

Abstract

Objectives: Idiopathic pulmonary fibrosis (IPF) is a fatal disease characterized by progressive respiratory failure. The chemokine receptor CXCR4 plays a pivotal role in migration of CXCR4 + progenitor cells to the lung. In this study, pulmonary CXCR4 expression was evaluated using quantitative positron emission tomography (PET), in order to test its role as a potential biomarker for IPF. Methods: PET with the specific CXCR4 ligand, gallium-68 ( 68 Ga)-pentixafor, was performed in 20 patients and compared with high-resolution CT (HRCT) of the chest, pulmonary function tests, and a clinical staging system (GAP index). In eight patients, follow-up scans were obtained following treatment with pirfenidon. Results: Patients showed variable degrees of CXCR4 upregulation in fibrotic areas. The average tracer uptake (SUV mean ) in fibrotic areas was 2.3±0.5 (range, 1.6-3.0). CXCR4 Tracer uptake was highest in the areas of honeycombing. Tracer uptake demonstrated a significant correlation with both GAP index (rs=0.6, p=0.01) and GAP stage/predicted mortality (rs=0.59, p=0.01) at baseline. Total lung capacity (rs=-0.59, p=0.02), but not DLCO (rs=-0.25, p=0.43) correlated with tracer uptake. In patients subsequently treated with pirfenidone, CXCR4 downregulation at the second PET imaging (week 6) correlated with treatment outcome (6 months). Conclusions: Targeted PET imaging with 68Ga-pentixafor identifies the CXCR4 expression pattern in the lung and correlates with clinical parameters known to be predictive of outcome. CXCR4 imaging may have a role in monitoring disease activity and may predict response to pirfenidone treatment in IPF.