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.
Near infrared (NIR) Raman spectroscopy provides a powerful method for quantitative histochemistry of human tissue and disease diagnosis. The feasibility and potential of this technique for in situ histochemical analysis of human coronary artery has been demonstrated and presented in other reports from our laboratory. In this work, we review recent results obtained with the NIR Raman spectroscopy on a variety of tissue types studied at the MIT Laser Biomedical Research Center. We have collected NIR Raman spectra from colon, bladder, breast, and carotid artery. For colon, bladder and breast, consistent differences between carcinoma and normal tissue spectra were observed. For colon and bladder, the spectral differences appear to be due to an increased content of nucleic acid in carcinomas, while the spectral changes in malignant breast tissue are associated with an increase of protein content. Spectra from carotid artery have similar features as those from aorta and coronary arteries. We also show some preliminary results obtained with a NIR Raman microspectroscopy setup with 20 micron lateral resolution. The biochemical distributions for normal and diseased regions on the same tissue samples are observed. The potential of using this NIR Raman spectroscopy for detection and characterization of carcinoma and atherosclerosis, is discussed.
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