Quantum dots targeted to vascular endothelial growth factor receptor 2 as a contrast agent for the detection of colorectal cancer

Abstract

Abstract. We successfully labeled colorectal cancer in vivo using quantum dots targeted to vascular endothelial growth factor receptor 2 (VEGFR2). Quantum dots with emission centered at 655 nm were bioconjugated to anti-VEGFR2 antibodies through streptavidin/biotin linking. The resulting QD655-VEGFR2 contrast agent was applied in vivo to the colon of azoxymethane (AOM) treated mice via lavage and allowed to incubate. The colons were then excised, cut longitudinally, opened to expose the lumen, and imaged en face using a fluorescence stereoscope. The QD655-VEGFR2 contrast agent produced a significant increase in contrast between diseased and undiseased tissues, allowing for fluorescence-based visualization of the diseased areas of the colon. Specificity was assessed by observing insignificant contrast increase when labeling colons of AOM-treated mice with quantum dots bioconjugated to isotype control antibodies, and by labeling the colons of saline-treated control mice. This contrast agent has a great potential for in vivo imaging of the colon through endoscopy.

Recent insights into nanotechnology development for detection and treatment of colorectal cancer

“…38 In another study, Carbary-Ganz et al 39 successfully labeled CRC in vivo using QDs targeted to VEGFR2. QDs with emission centered at 655 nm were bioconjugated to anti-VEGFR2 antibodies through streptavidin/biotin linking.…”

“…QDs with emission centered at 655 nm were bioconjugated to anti-VEGFR2 antibodies through streptavidin/biotin linking. 39 The resulting QD655-VEGFR2 contrast agent was functional in vivo and localized to the colon of azoxymethane-treated mice following lavage and incubation. This QD655-VEGFR2 contrast agent significantly enhanced the contrast between diseased and normal tissues.…”

“…This contrast agent shows great possibility for in vivo endoscopic imaging of the colon. 39 Using the subtractive Cell-SELEX technology under selective conditions, Li et al 40 produced a panel of seven aptamers (Apts) that specifically bind metastatic CRC cells (LoVo cells) and some other metastatic cancer cell lines with high affinity, thereby offering broad-spectrum specific recognition of metastatic cancer cells. This study demonstrated that Apts selected from single Cell-SELEX can be individually functionalized for various purposes according to the biochemical properties of the targets, thereby increasing the advantages of the Cell-SELEX approach.…”

In vivomolecular imaging of colorectal cancer using quantum dots targeted to vascular endothelial growth factor receptor 2 and optical coherence tomography/laser-induced fluorescence dual-modality imaging

“…[46][47][48] Recently, our group demonstrated that QDot655 targeted to VEGFR2 (QD655-VEGFR2) can be applied to the colon of carcinogen-treated mice in vivo and provides significantly increased contrast between diseased and undiseased tissue ex vivo (explanted) with high sensitivity and specificity compared to a control contrast agent. 49 This quantum dot is readily available, easy to conjugate, emits in a region of light that has less endogenous emission interference, and is compatible with all commonly used optical coherence tomography (OCT) systems. Thus, evidence exists that quantum dots bioconjugated to VEGFR2 antibodies can provide a mechanism for evaluating the molecular changes of colorectal tumors in vivo.…”

“…We have previously shown that QD655-VEGFR2 can be used to label adenoma expressing VEGFR2 through in vivo labeling and ex vivo fluorescence imaging with high sensitivity and specificity, and also using the OCT/LIF microendoscope ex vivo. 49 Quantum dot fluorescence in the colon should coordinate with VEGFR2 expressing adenoma. OCT provided the gold standard for the presence of adenoma with immunohistochemistry (IHC) as a gold standard for VEGFR2 expression.…”