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Proceedings Paper

EGF-conjugated near-infrared quantum dots as nanoprobes for in-vivo imaging of EGFR expression
Author(s): Parmeswaran Diagaradjane; Jacobo M. Orenstein-Cardona; Norman E Colón-Casasnovas; Amit Deorukhkar; Shujun Shentu; Norihito Kuno; David L. Schwartz; Juri G. Gelovani; Sunil Krishnan
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Paper 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.

Paper Details

Date Published: 22 February 2008
PDF: 9 pages
Proc. SPIE 6866, Colloidal Quantum Dots for Biomedical Applications III, 68660R (22 February 2008); doi: 10.1117/12.763985
Show Author Affiliations
Parmeswaran Diagaradjane, The Univ. of Texas M.D. Anderson Cancer Ctr. (United States)
Jacobo M. Orenstein-Cardona, The Univ. of Texas M.D. Anderson Cancer Ctr. (United States)
Norman E Colón-Casasnovas, The Univ. of Texas M.D. Anderson Cancer Ctr. (United States)
Amit Deorukhkar, The Univ. of Texas M.D. Anderson Cancer Ctr. (United States)
Shujun Shentu, The Univ. of Texas M.D. Anderson Cancer Ctr. (United States)
Norihito Kuno, The Univ. of Texas M.D. Anderson Cancer Ctr. (United States)
David L. Schwartz, The Univ. of Texas M.D. Anderson Cancer Ctr. (United States)
Juri G. Gelovani, The Univ. of Texas M.D. Anderson Cancer Ctr. (United States)
Sunil Krishnan, The Univ. of Texas M.D. Anderson Cancer Ctr. (United States)


Published in SPIE Proceedings Vol. 6866:
Colloidal Quantum Dots for Biomedical Applications III
Marek Osinski; Thomas M. Jovin; Kenji Yamamoto, Editor(s)

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