Novel PET radiotracers [¹⁸F]AF78 and [¹⁸F]11c demonstrated high affinity for NET and CXCR2 respectively, though in vivo studies revealed species-dependent differences in uptake.
The development of novel fluorine-18 labeled radiotracers targeting NET and CXCR2 expands the repertoire of PET imaging agents for cardiovascular disease, though species-dependent differences highlight translational challenges.
This dissertation addresses the development of novel positron emission tomography (PET) radiotracers for cardiovascular imaging, focusing on the identification and targeting of new molecular biomarkers. In particular, the norepinephrine transporter (NET) and the chemokine receptor CXCR2 were investigated as key targets for imaging sympathetic nervous system activity and inflammatory processes, both of which play central roles in cardiovascular disease. The first part of this work presents the development and characterization of the fluorine-18 labeled radiotracer ¹⁸FAF78, designed for NET imaging. Through a combination of in silico modeling, in vitro uptake assays, and in vivo PET studies, the tracer demonstrated high affinity comparable to endogenous norepinephrine. Structure–activity relationship analyses revealed that small substituents enhance NET binding, while larger or more polar modifications reduce affinity. A major finding of this work is the identification of a dual uptake mechanism involving both NET and organic cation transporters (OCTs), which significantly influences tracer biodistribution and cardiac imaging outcomes. The second part focuses on the development of the first fluorine-18 labeled CXCR2-targeting radiotracer, ¹⁸F11c, for imaging neutrophil infiltration following myocardial infarction. In vitro studies confirmed high specificity and binding affinity to CXCR2, while in vivo experiments revealed species-dependent differences in tracer uptake, highlighting challenges in translational imaging. Overall, this work expands the repertoire of PET radiotracers for cardiovascular applications and provides important insights into molecular imaging mechanisms. The findings contribute to the optimization of next-generation radiotracers with improved specificity and sensitivity, supporting future advances in non-invasive diagnostics and personalized medicine.
Saskia Mühlig (Thu,) conducted a other in Cardiovascular disease. [¹⁸F]AF78 and [¹⁸F]11c was evaluated on Tracer affinity, specificity, and biodistribution. Novel PET radiotracers [¹⁸F]AF78 and [¹⁸F]11c demonstrated high affinity for NET and CXCR2 respectively, though in vivo studies revealed species-dependent differences in uptake.