Early and accurate tumor detection is key to successful cancer management. Nanotechnology-based biomedical imaging offers strong potential to enhance tumor detection through improved sensitivity and specificity, particularly via the enhanced permeability and retention (EPR) effect. However, suboptimal biodistribution of imaging agents is often associated with a pronounced liver retention. Fluorinated compounds, though rare in nature, provide unique physicochemical properties thanks to the high electronegativity of fluorine, its strong inductive effect, and the low polarizability of the C-F bond, conferring exceptional chemical stability and biological inertness. Here, we report a fluorinated supramolecular dendrimer nanosystem for tumor imaging using positron emission tomography (PET). This system was constructed via the self-assembly of an amphiphilic fluorinated dendrimer radiolabeled with gallium-68, a positron-emitting radionuclide commonly used for PET. This fluorinated radiotracer exhibited a nanoscale size and had high radiochemical purity and stability. Compared to its non-fluorinated analogue, the fluorinated system showed reduced liver accumulation, improved pharmacokinetics, and significantly enhanced tumor uptake in orthotopic and ectopic mouse xenograft models of glioblastoma and pancreatic adenocarcinoma. These results demonstrate that fluorination is a powerful strategy to optimize pharmacokinetics and biodistribution of imaging agents, enabling more accurate and effective tumor detection.
Louis et al. (Tue,) studied this question.