Targeted 89Zr-Labeled metallofluorocarbon nanoemulsion for carcinoembryonic antigen PET

Background Elevated levels of carcinoembryonic antigen (CEA) are strongly associated with several malignancies, including colorectal and hepatic adenocarcinomas, making CEA a clinically valuable biomarker. Targeted molecular imaging using positron emission tomography (PET) in combination with CEA-specific tracers offers the potential for improved tumor detection and longitudinal disease monitoring. Methods We developed a nanoemulsion (NE) platform incorporating a fluorous-encapsulated radiometal (FERM) chelate, in which 89 Zr is complexed to a fluorinated hydroxamic acid chelator sequestered within the fluorous core of (~200 nm) NE droplets. CEA targeting was achieved using a humanized anti-CEA antibody functionalized with an azide group and conjugated via copper-free click chemistry to “click-ready” NEs bearing dibenzocyclooctyne (DBCO) moieties within the surfactant layer. Results In vitro studies demonstrated specific binding of the targeted NEs in both protein- and cell-based assays using LS174T cells. In vivo PET/CT imaging of LS174T xenografts in nude mice revealed selective accumulation of the antibody-functionalized 89 Zr-labeled NE in tumors within 4–120 h post injection, with target specificity validated by immunohistopathology. Clearance occurred predominantly through the spleen and liver, consistent with reticuloendothelial system uptake. Conclusion Click-ready FERM NEs form a stable colloidal suspension of nanoscale droplets with a high radiometal payload and PET sensitivity. This targeted imaging platform shows strong potential for early detection and monitoring of cancer-associated biomarkers such as CEA. The modular design enables facile adaptation to a wide range of targeting ligands, supporting applications in molecular imaging and therapeutic delivery.