In vivo evaluation of 64Cu labeled PEGylated shell crosslinked nanoparticles (SCKs) as candidates for imaging and drug delivery

174 Objectives: Nanoparticles (NPs) can be multi-functionalized for in vivo targeting, imaging, and drug delivery. The goal of this work was to design nanocarriers able to avoid the mononuclear phagocyte system (MPS) for nanomedical application. 64Cu was used to track the in vivo fate of these nanostructures in normal rodents. Methods: Amphiphilic diblock copolymers were conjugated with 2 DOTA and 0, 1, 2.4 or 5.5 PEG2000 chains per polymer and used to synthesize SCK1-4. After 64Cu-labeling, the SCK blood retention and MPS uptake were evaluated in normal rats (20-25 μg/kg) and mice (0.15-0.3 mg/kg) with biodistribution techniques and small animal PET imaging, respectively. Results: Increasing the amount of PEG per polymer chain prolonged the SCK blood retention (from 0.05 to 3.5 %ID/g at 1 h p.i.) and lowered the MPS uptake. Also, changes in the SCK surface density due to 20% (SCK4) or 50% (SCK5) crosslinking had the same influence. PET imaging confirmed the biodistribution data, as only the heart of the mice injected with SCK5 was clearly visible up to 24 h p.i. Conclusions: 64Cu-labeling and PET are excellent tools to evaluate NPs in vivo. The stealth properties of SCKs were finely tuned by choosing the appropriate number of PEG grafts or by modifying the surface density. These results suggest that SCKs can be employed as a platform for drug delivery and molecular imaging. Research Support: This material is based upon work supported by the NIH as a Program of Excellence in Nanotechnology (HL080729). The production of 64Cu is supported by a grant from the NCI (CA86307).