TY - GEN
T1 - EGF-conjugated Near-infrared quantum dots as nanoprobes for in-vivo imaging of EGFR expression
AU - Diagaradjane, Parmeswaran
AU - Orenstein-Cardona, Jacobo M.
AU - Cólon-Casasnovas, Norman E.
AU - Deorukhkar, Amit
AU - Shentu, Shujun
AU - Kuno, Norihito
AU - Schwartz, David L.
AU - Gelovani, Juri G.
AU - Krishnan, Sunil
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2008
Y1 - 2008
N2 - 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. Nearinfrared 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 (l-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.
AB - 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. Nearinfrared 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 (l-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.
KW - EGFR
KW - Molecular imaging
KW - Nanoprobe
KW - Quantum dots
UR - http://www.scopus.com/inward/record.url?scp=43249086248&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=43249086248&partnerID=8YFLogxK
U2 - 10.1117/12.763985
DO - 10.1117/12.763985
M3 - Conference contribution
AN - SCOPUS:43249086248
SN - 9780819470416
T3 - Progress in Biomedical Optics and Imaging - Proceedings of SPIE
BT - Colloidal Quantum Dots for Biomedical Applications III
T2 - Colloidal Quantum Dots for Biomedical Applications III
Y2 - 19 January 2008 through 21 January 2008
ER -