Evaluation of modified PEG-anilinoquinazoline derivatives as potential agents for EGFR imaging in cancer by small animal PET

Maria A. Pantaleo, Eyal Mishani, Cristina Nanni, Lorena Landuzzi, Stefano Boschi, Giordano Nicoletti, Samar Dissoki, Paola Paterini, Pier Poalo Piccaluga, Filippo Lodi, Pier Luigi Lollini, Stefano Fanti, Guido Biasco

Research output: Contribution to journalArticlepeer-review


Purpose: The in vivo evaluation of three modified polyethylene glycol (PEG)-anilinoquinazoline derivatives labeled with 124I, 18F, and 11C 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 18F-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, respectively (p∈=∈0.00008). Similarly, the microvessel grades were generally higher in the U87GM group (p∈=∈0.002). Total EGFR amount was higher in U87MG than U138MG masses (p∈=∈0.001), but the ratio of activated (pY1068) to total EGFR did not differ (p∈=∈0.95). Conclusions: PEGylated tracers labeled with 11C, 124I, and 18F showed no significant difference in uptake between U138MG and U87MG glioblastoma xenograft mice. The tracer binding with EGFR could be influenced by activation of the tyrosine kinase portion of the receptor which was similar in U138MG and U87MG. Despite these results, these tracers should be investigated in animal models with mutant EGFR genes to determine whether aberrant receptor function plays a role in tumor uptake.

Original languageEnglish
Pages (from-to)616-625
Number of pages10
JournalMolecular Imaging and Biology
Issue number6
Publication statusPublished - Dec 2010


  • Epidermal growth factor receptor (EGFR)
  • Small animal PET
  • Tyrosine kinase (TK) inhibitors

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Radiology Nuclear Medicine and imaging


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