| Evaluation of modified PEG-anilinoquinazoline derivatives as potential agents for EGFR imaging in cancer by small animal PET. | |
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MedLine Citation:
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PMID: 20379787 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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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, 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 (11)C, (124)I, and (18)F 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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Authors:
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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 |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging Volume: 12 ISSN: 1860-2002 ISO Abbreviation: Mol Imaging Biol Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-12 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101125610 Medline TA: Mol Imaging Biol Country: United States |
Other Details:
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Languages: eng Pagination: 616-25 Citation Subset: IM |
Affiliation:
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Department of Hematology and Oncological Sciences L.A. Serganoli, Sant'Orsola-Malpighi Hospital, University of Bologna, Via Massarenti 9, Bologna, Italy. maria.pantaleo@unibo.it |
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