PURPOSE: To develop and validate an optical imaging nanoprobe for the discrimination of epidermal growth factor (EGF) receptor (EGFR)-overexpressing tumors from surrounding normal tissues that also expresses EGFR. EXPERIMENTAL DESIGN: Near-infrared (NIR) quantum dots (QD) were coupled to EGF using thiol-maleimide conjugation to create EGF-QD nanoprobes. In vitro binding affinity of these nanoprobes and unconjugated QDs was evaluated in a panel of cell lines, with and without anti-EGFR antibody pretreatment. Serial optical imaging of HCT116 xenograft tumors was done after systemic injection of QD and EGF-QD. RESULTS: EGF-QD showed EGFR-specific binding in vitro. In vivo imaging showed three distinct phases, tumor influx ( approximately 3 min), clearance ( approximately 60 min), and accumulation (1-6 h), of EGF-QD nanoprobes. Both QD and EGF-QD showed comparable nonspecific rapid tumor influx and clearance followed by attainment of an apparent dynamic equilibrium at approximately 60 min. Subsequently (1-6 h), whereas QD concentration gradually decreased in tumors, EGF-QDs progressively accumulated in tumors. On delayed imaging at 24 h, tumor fluorescence decreased to near-baseline levels for both QD and EGF-QD. Ex vivo whole-organ fluorescence, tissue homogenate fluorescence, and confocal microscopic analyses confirmed tumor-specific accumulation of EGF-QD at 4 h. Immunofluorescence images showed diffuse colocalization of EGF-QD fluorescence within EGFR-expressing tumor parenchyma compared with patchy perivascular sequestration of QD. CONCLUSION: These results represent the first pharmacokinetic characterization of a robust EGFR imaging nanoprobe. The measurable contrast enhancement of tumors 4 h after systemic administration of EGF-QD and its subsequent normalization at 24 h imply that this nanoprobe may permit quantifiable and repetitive imaging of EGFR expression.
PURPOSE: To develop and validate an optical imaging nanoprobe for the discrimination of epidermal growth factor (EGF) receptor (EGFR)-overexpressing tumors from surrounding normal tissues that also expresses EGFR. EXPERIMENTAL DESIGN: Near-infrared (NIR) quantum dots (QD) were coupled to EGF using thiol-maleimide conjugation to create EGF-QD nanoprobes. In vitro binding affinity of these nanoprobes and unconjugated QDs was evaluated in a panel of cell lines, with and without anti-EGFR antibody pretreatment. Serial optical imaging of HCT116 xenograft tumors was done after systemic injection of QD and EGF-QD. RESULTS: EGF-QD showed EGFR-specific binding in vitro. In vivo imaging showed three distinct phases, tumor influx ( approximately 3 min), clearance ( approximately 60 min), and accumulation (1-6 h), of EGF-QD nanoprobes. Both QD and EGF-QD showed comparable nonspecific rapid tumor influx and clearance followed by attainment of an apparent dynamic equilibrium at approximately 60 min. Subsequently (1-6 h), whereas QD concentration gradually decreased in tumors, EGF-QDs progressively accumulated in tumors. On delayed imaging at 24 h, tumor fluorescence decreased to near-baseline levels for both QD and EGF-QD. Ex vivo whole-organ fluorescence, tissue homogenate fluorescence, and confocal microscopic analyses confirmed tumor-specific accumulation of EGF-QD at 4 h. Immunofluorescence images showed diffuse colocalization of EGF-QD fluorescence within EGFR-expressing tumor parenchyma compared with patchy perivascular sequestration of QD. CONCLUSION: These results represent the first pharmacokinetic characterization of a robust EGFR imaging nanoprobe. The measurable contrast enhancement of tumors 4 h after systemic administration of EGF-QD and its subsequent normalization at 24 h imply that this nanoprobe may permit quantifiable and repetitive imaging of EGFR expression.
Authors: Y Waerzeggers; P Monfared; T Viel; A Faust; K Kopka; M Schäfers; B Tavitian; A Winkeler; A Jacobs Journal: Br J Radiol Date: 2011-12 Impact factor: 3.039
Authors: Jason H Sakamoto; Anne L van de Ven; Biana Godin; Elvin Blanco; Rita E Serda; Alessandro Grattoni; Arturas Ziemys; Ali Bouamrani; Tony Hu; Shivakumar I Ranganathan; Enrica De Rosa; Jonathan O Martinez; Christine A Smid; Rachel M Buchanan; Sei-Young Lee; Srimeenakshi Srinivasan; Matthew Landry; Anne Meyn; Ennio Tasciotti; Xuewu Liu; Paolo Decuzzi; Mauro Ferrari Journal: Pharmacol Res Date: 2010-01-05 Impact factor: 7.658
Authors: Heling Zhou; Kate Luby-Phelps; Bruce E Mickey; Amyn A Habib; Ralph P Mason; Dawen Zhao Journal: PLoS One Date: 2009-11-30 Impact factor: 3.240