EGF-conjugated near-infrared quantum dots as nanoprobes for in-vivo imaging of EGFR expression

Parmeswaran Diagaradjane; Jacobo M. Orenstein-Cardona; Norman E Colón-Casasnovas; Amit Deorukhkar; Shujun Shentu; Norihito Kuno; David L. Schwartz; Juri G. Gelovani; Sunil Krishnan

doi:10.1117/12.763985

22 February 2008 EGF-conjugated near-infrared quantum dots as nanoprobes for in-vivo imaging of EGFR expression

Parmeswaran Diagaradjane, Jacobo M. Orenstein-Cardona, Norman E Colón-Casasnovas, Amit Deorukhkar, Shujun Shentu, Norihito Kuno, David L. Schwartz, Juri G. Gelovani, Sunil Krishnan

Author Affiliations +

Proceedings Volume 6866, Colloidal Quantum Dots for Biomedical Applications III; 68660R (2008) https://doi.org/10.1117/12.763985
Event: SPIE BiOS, 2008, San Jose, California, United States

Abstract

Noninvasive imaging of epidermal growth factor (EGF) receptor (EGFR) expression can provide valuable molecular information that could aid diagnostic and therapeutic decisions, particularly with targeted cancer therapies utilizing anti-EGFR antibodies. In this study we report on the development and validation of a nanoprobe for in-vivo imaging and discrimination of EGFR-overexpressing tumors from surrounding normal tissues that also expresses EGFR. Near-infrared quantum dots (QDs) were coupled to EGF using thiol-maleimide conjugation to create EGF-QD nanoprobes. These nanoprobes demonstrated excellent in-vitro and in-vivo binding affinity. In-vivo imaging demonstrated three distinct phases of tumor influx (~3min), clearance (~60min) and accumulation (1-6hrs) of EGF-QD nanoprobes. Both QD and EGF-QD demonstrated non-specific rapid tumor influx and clearance followed by an apparent dynamic equilibrium at ~60min. Subsequently (1-6hrs), while QD concentration gradually decreased in tumors, EGF-QDs progressively accumulated in tumors. At 24hrs, tumor fluorescence decreased to near baseline levels for both QD and EGF-QD. Ex vivo whole-organ, tissue-homogenate fluorescence, confocal microscopy and immunofluorescence staining confirmed tumor-specific accumulation of EGF-QD nanoprobes at an early time-point (4hrs). The favorable pharmacokinetics, the ability to discriminate EGFR-overexpressing tumors from surrounding normal tissues using low concentration (10-pmol) of EGF-QD nanoprobe underscores the clinical relevance of this probe to evaluate therapeutic intervention.

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Parmeswaran Diagaradjane, Jacobo M. Orenstein-Cardona, Norman E Colón-Casasnovas, Amit Deorukhkar, Shujun Shentu, Norihito Kuno, David L. Schwartz, Juri G. Gelovani, and Sunil Krishnan "EGF-conjugated near-infrared quantum dots as nanoprobes for in-vivo imaging of EGFR expression", Proc. SPIE 6866, Colloidal Quantum Dots for Biomedical Applications III, 68660R (22 February 2008); https://doi.org/10.1117/12.763985

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