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Molecular Imaging and Biology
Published in: Molecular Imaging and Biology 6/2010

Open Access 01-12-2010 | Research Article

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

Authors: 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

Published in: Molecular Imaging and Biology | Issue 6/2010

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Abstract

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.
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Metadata
Title
Evaluation of Modified PEG-Anilinoquinazoline Derivatives as Potential Agents for EGFR Imaging in Cancer by Small Animal PET
Authors
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
Publication date
01-12-2010
Publisher
Springer-Verlag
Published in
Molecular Imaging and Biology / Issue 6/2010
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI
https://doi.org/10.1007/s11307-010-0315-z

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