1. Synthesis and Analysis of 64 Cu-Labeled GE11-Modified Polymeric Micellar Nanoparticles for EGFR-Targeted Molecular Imaging in a Colorectal Cancer Model.
- Author
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Paiva I, Mattingly S, Wuest M, Leier S, Vakili MR, Weinfeld M, Lavasanifar A, and Wuest F
- Subjects
- Animals, Cell Line, Tumor, Humans, Isotope Labeling, Mice, Mice, Inbred BALB C, Micelles, Nanoparticles, Polymers metabolism, Positron-Emission Tomography, Radiopharmaceuticals pharmacokinetics, Colorectal Neoplasms diagnostic imaging, Copper Radioisotopes pharmacokinetics, ErbB Receptors antagonists & inhibitors, Molecular Imaging methods, Peptides metabolism, Radiopharmaceuticals chemical synthesis
- Abstract
Polymeric micellar nanoparticles represent versatile and biocompatible platforms for targeted drug delivery. However, tracking their biodistribution, stability, and clearance profile in vivo is challenging. The goal of this study was to prepare surface-modified micelles with peptide GE11 for targeting the epidermal growth factor receptor (EGFR). In vitro fluorescence studies demonstrated significantly higher internalization of GE11 micelles into EGFR-expressing HCT116 colon cancer cells versus EGFR-negative SW620 cells. Azo coupling chemistry of tyrosine residues in the peptide backbone with aryl diazonium salts was used to label the micelles with radionuclide
64 Cu for positron emission tomography (PET) imaging. In vivo analysis of64 Cu-labeled micelles showed prolonged blood circulation and predominant hepatobiliary clearance. The biodistribution profile of EGFR-targeting GE11 micelles was compared with nontargeting HW12 micelles in HCT116 tumor-bearing mice. PET revealed increasing tumor-to-muscle ratios for both micelles over 48 h. Accumulation of GE11-containing micelles in HCT116 tumors was higher compared to HW12-decorated micelles. Our data suggest that the efficacy of image-guided therapies with micellar nanoparticles could be enhanced by active targeting, as demonstrated with cancer biomarker EGFR.- Published
- 2020
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