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

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

Research output: Chapter in Book/Report/Conference proceedingConference contribution

2 Citations (Scopus)

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. 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.

Original languageEnglish (US)
Title of host publicationColloidal Quantum Dots for Biomedical Applications III
Volume6866
DOIs
StatePublished - May 15 2008
EventColloidal Quantum Dots for Biomedical Applications III - San Jose, CA, United States
Duration: Jan 19 2008Jan 21 2008

Other

OtherColloidal Quantum Dots for Biomedical Applications III
CountryUnited States
CitySan Jose, CA
Period1/19/081/21/08

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Nanoprobes
Semiconductor quantum dots
Infrared radiation
Imaging techniques
Tumors
Tissue
Epidermal Growth Factor
Fluorescence
Pharmacokinetics
Confocal microscopy
Antibodies

All Science Journal Classification (ASJC) codes

  • Engineering(all)

Cite this

Diagaradjane, P., Orenstein-Cardona, J. M., Cólon-Casasnovas, N. E., Deorukhkar, A., Shentu, S., Kuno, N., ... Krishnan, S. (2008). EGF-conjugated Near-infrared quantum dots as nanoprobes for in-vivo imaging of EGFR expression. In Colloidal Quantum Dots for Biomedical Applications III (Vol. 6866). [68660R] https://doi.org/10.1117/12.763985

EGF-conjugated Near-infrared quantum dots as nanoprobes for in-vivo imaging of EGFR expression. / Diagaradjane, Parmeswaran; Orenstein-Cardona, Jacobo M.; Cólon-Casasnovas, Norman E.; Deorukhkar, Amit; Shentu, Shujun; Kuno, Norihito; Schwartz, David; Gelovani, Juri G.; Krishnan, Sunil.

Colloidal Quantum Dots for Biomedical Applications III. Vol. 6866 2008. 68660R.

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Diagaradjane, P, Orenstein-Cardona, JM, Cólon-Casasnovas, NE, Deorukhkar, A, Shentu, S, Kuno, N, Schwartz, D, Gelovani, JG & Krishnan, S 2008, EGF-conjugated Near-infrared quantum dots as nanoprobes for in-vivo imaging of EGFR expression. in Colloidal Quantum Dots for Biomedical Applications III. vol. 6866, 68660R, Colloidal Quantum Dots for Biomedical Applications III, San Jose, CA, United States, 1/19/08. https://doi.org/10.1117/12.763985
Diagaradjane P, Orenstein-Cardona JM, Cólon-Casasnovas NE, Deorukhkar A, Shentu S, Kuno N et al. EGF-conjugated Near-infrared quantum dots as nanoprobes for in-vivo imaging of EGFR expression. In Colloidal Quantum Dots for Biomedical Applications III. Vol. 6866. 2008. 68660R https://doi.org/10.1117/12.763985
Diagaradjane, Parmeswaran ; Orenstein-Cardona, Jacobo M. ; Cólon-Casasnovas, Norman E. ; Deorukhkar, Amit ; Shentu, Shujun ; Kuno, Norihito ; Schwartz, David ; Gelovani, Juri G. ; Krishnan, Sunil. / EGF-conjugated Near-infrared quantum dots as nanoprobes for in-vivo imaging of EGFR expression. Colloidal Quantum Dots for Biomedical Applications III. Vol. 6866 2008.
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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. 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.",
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