Synthesis and Evaluation of 18F-Radiotracers for Imaging of Pulmonary Fibrosis

Abstract

Pulmonary fibrosis is a progressive disease with limited diagnostic tools for early detection. Positron Emission Tomography (PET) enables molecular imaging using radiotracers labeled with fluorine-18, a radionuclide offering optimal half-life and imaging resolution. This work aimed to design and synthesize novel radiotracers targeting human neutrophil elastase (HNE), a key enzyme implicated in fibrotic remodeling. Several candidate molecules were prepared and evaluated for chemical stability and biological activity. The oxazinone derivative demonstrated significant inhibitory potency toward HNE and acceptable stability under radiolabeling conditions, justifying its selection for precursor synthesis. An arylstannane derivative was successfully obtained and submitted to automated [18F] fluorination, achieving a radiochemical conversion of 85% and a pre-purification non-decay corrected yield of 53%. These results confirm the feasibility of the proposed strategy and the potential of PET imaging in fibrosis diagnosis. Future work will focus on purification optimization and preclinical validation to advance fibrosis imaging.