(350u) Investigation of the Effects of Surface Coatings on the Properties and Biodistribution of 64-Cu Labeled Nanoparticles for Use in Mouse Pancreatic Cancer Model

Positron Emission Tomography (PET) is a biomedical imaging modality that can construct highly detailed images of target regions by detecting gamma rays produced from the collision of positrons and electrons within a patient’s body. Nanoparticles (NPs) acting as contrast agents have improved the sensitivity of PET-targeted imaging, as localized clusters of NPs increase the signal intensity in a particular region. A prominent concern that comes with the use of PET-active NPs relates to their biodistribution, which is affected by particle size and surface coatings. Previously, Lu et al. has optimized use of the hydrophobic molecule 1,4,8,11,15,18,22,25-Octabutoxy-phthalocyanine (“762Pc”) for chelation of 64-Cu into 762-core NPs to create PET-active NPs with a poly-ethylene glycol (PEG) surface coating. However, little work has been done on the effect of other surface coatings on copper loading for NP radiolabeling. Here, we: (1) formed and characterized the stability of NPs with different surface coatings (2) optimized their copper chelation kinetics (3) evaluated biodistribution in an animal model. Toward this end, we utilized the self-assembly Flash NanoPrecipitation (FNP) process to formulate water-dispersible, poly-ethylene glycol (PEG), poly-acrylic acid (PAA) and poly-dimethylethylmethacrylate (DMEMA)-coated NPs. These coatings were selected based on varying charges imposed on the nanoparticle surface. By tuning the core concentration during FNP, 762Pc encapsulated particles were formed with sizes that can be tuned from 90 to 160 nm. 64-Cu radiolabeling trials on these NPs revealed that PEG and PAA-coated NPs took up > 99% of the initial 64-Cu activity after a 3- hour incubation in a pH 5.5 buffer at 37°C - reaching over 500uCi of activity. Subsequent animal studies will be conducted in a mice model to evaluate how surface coating and size affects NP biodistribution using PET. We hope that these results demonstrate the potential of different surface coatings to be used in PET-imaging and diagnostic applications.