Chelator-Free Labeling of Metal Oxide Nanostructures with Zirconium-89 for Positron Emission Tomography Imaging.

Radiolabeling of molecules or nanoparticles to form imaging probes is critical for positron emission tomography (PET) imaging, which, with high sensitivity and the ability for quantitative imaging, has been widely used in the clinic. While conventional radiolabeling often employs chelator molecules, a general method for chelator-free radiolabeling of a wide range of materials remains to be developed. Herein, we determined that 10 different types of metal oxide (MO M = Gd, Ti, Te, Eu, Ta, Er, Y, Yb, Ce, or Mo, x = 1-2, y = 2-5) nanomaterials with polyethylene glycol (PEG) modification could be labeled with Zr, a PET tracer, via a simple yet general chelator-free radiolabeling method upon simple mixing. High-labeling yields and good serum stabilities are achieved with this method, owing to the strong bonding between oxyphilic Zr with oxygen atoms on the MO surface. Selecting Zr-GdO-PEG as a multimodal imaging probe, we have successfully demonstrated in vivo PET imaging of draining lymph nodes, which are also visualized under magnetic resonance imaging, showing advantages over free Zr in the mapping of draining lymph node networks. Our work describes a general and simple method for chelator-free radiolabeling of metal oxide nanostructures, which is promising for the development of multifunctional nanoprobes in biomedical imaging.