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