Copper Loading of Pre-Formed Nanoparticles for PET-Imaging Applications.

Nanoparticles (NP) are promising contrast agents for positron emission tomography (PET) radionuclide imaging that can increase signal intensity by localizing clusters of PET radionuclides together. However, methods to load NPs with PET radionuclides suffer from harsh loading conditions, poor loading efficacies, or result in NP surface modifications that alter targeting in vivo. We present the formation of water dispersible and polyethylene glycol coated (PEG) NPs that encapsulate phthalocyanines into NP cores at greater than 50% wt loading, using the self-assembly technique Flash NanoPrecipitation. Particles from 70-160 nm are produced. Phthalocyanine NPs rapidly and spontaneously chelate metals under mild conditions, and can act as sinks for PET radionuclides such as 64-Cu to produce PET-active NPs. NPs chelate copper(II) with characteristic rates of 1,845 M hr at pH 6 and 37ºC, which produced >90% radionuclide chelation within one hour. NP physical properties, such as core composition, core fluidity, and size can be tuned to modulate chelation kinetics. These NPs retain Cu even in the presence of the strong chelator, ethylene diamine tetraacetic acid (EDTA). The development of these constructs for rapid and facile radionuclide labeling expands the applications of NP-based PET imaging.