Evaluation of Modified PEG-Anilinoquinazoline Derivatives as Potential Agents for EGFR Imaging in Cancer by Small Animal PET

Purpose: The in vivo evaluation of three modified polyethylene glycol (PEG)-anilinoquinazoline derivatives labeled with 124 I, 18 F, and 11 C as potential positron emission tomography (PET) bioprobes for visualizing epidermal growth factor receptor (EGFR) in cancer using small animal PET. Procedures: Xenograft mice with the human glioblastoma cell lines U138MG (lacking EGFR expression) and U87MG.wtEGFR (transfected with an overexpressing human wild-type EGFR gene) were used. Static and dynamic PET imaging was conducted for all three PEGylated compounds. Tumor necrosis, microvessel density, and EGFR levels were evaluated by histopathology and enzyme-linked immunosorbent assay. Results: Nineteen animal models were generated (two U138MG, three U87MG, 14 with both U138MG and U87MG bilateral masses). In static images, a slight increase in tracer uptake was observed in tumors, but in general, there was no retention of tracer uptake over time and no difference in uptake between U138MG and U87MG masses. In addition, no significant uptake was demonstrated in dynamic scans of the 18 F-PEG tracer. No necrosis was present except in four animals. MVD was 9.6 and 48 microvessels/×400 field in the U138GM and U87GM masses

Enhanced EGFR Targeting Activity of Plasmonic Nanostructures with Engineered GE11 Peptide

Targeting activity is an important goal of nanomedicine and antibodies have been considered the natural molecules for such a task. However, their possible immunogenic activity and their cost have suggested finding other valid substitutes. Small molecules like peptides can be an alternative source of targeting agents, even if, as single molecules, their binding affinity is usually not as good as antibodies. GE11 is a small dodecapeptide that displays specific binding to the epidermal growth factor receptor (EGFR) and low mitogenic activity. The present work shows that an appropriate organization of thousands of PEG chains functionalized with GE11 on clusters of naked gold nanoparticles, obtained by laser ablation in water, achieves a better targeting activity than that recorded with nanoparticles decorated with the specific anti-EGFR antibody Cetuximab (C225), already used in the clinic. The insertion of a cationic spacer between the polymeric part of the ligand and the targeting peptide allows for a proper presentation of GE11 on the surface of the nanosystems, showing with very specific SERRS signals, the possibility of achieving, with colorectal cancer cells, at least 90% for sensitivity and specificity. Molecular dynamic calculations suggest that subtle differences in the exposition of the peptide on a PEG sea are important for the targeting activity