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

Abstract

Optical coherence tomography/laser induced fluorescence (OCT/LIF) dual-modality imaging allows for minimally invasive, nondestructive endoscopic visualization of colorectal cancer in mice. This technology enables simultaneous longitudinal tracking of morphological (OCT) and biochemical (fluorescence) changes as colorectal cancer develops, compared to current methods of colorectal cancer screening in humans that rely on morphological changes alone. We have shown that QDot655 targeted to vascular endothelial growth factor receptor 2 (QD655-VEGFR2) can be applied to the colon of carcinogen-treated mice and provides significantly increased contrast between the diseased and undiseased tissue with high sensitivity and specificity ex vivo. QD655-VEGFR2 was used in a longitudinal in vivo study to investigate the ability to correlate fluorescence signal to tumor development. QD655-VEGFR2 was applied to the colon of azoxymethane (AOM-) or saline-treated control mice in vivo via lavage. OCT/LIF images of the distal colon were taken at five consecutive time points every three weeks after the final AOM injection. Difficulties in fully flushing unbound contrast agent from the colon led to variable background signal; however, a spatial correlation was found between tumors identified in OCT images, and high fluorescence intensity of the QD655 signal, demonstrating the ability to detect VEGFR2 expressing tumors in vivo.

Recent advances in biosensor development for the detection of cancer biomarkers

“…Among different nanomaterials, nanoparticles are extensively used in cancer biosensors as they exhibit enhanced surface area, size and shape tunable optical and electronic properties (Ding et al, 2013). The use of semiconductor quantum dots (QDs) is also progressively increasing in cancer diagnosis (Cabral Filho et al, 2015;Carbary-Ganz et al, 2015). Their unusual optical properties like broad excitation spectra and narrow emission spectra allow their use in high throughput multiplexed detection (Li and Zhu, 2013;Tian et al, 2012).…”

Nanotechnology in Colorectal Cancer for Precision Diagnosis and Therapy

“…A highly sensitive and specific technology was developed, which enables concurrent detection of biochemical fluorescence and morphological changes during CRC progression and development using optical coherence tomography or laser-induced tomography that allows nondestructive internal visualization of CRC (Carbary-Ganz et al, 2015). A probe QDot655 specific to vascular endothelial growth factor receptor 2 (QD655-GEGFR2) restricted to the colon used in carcinogen-treated mice and provides significantly high contrast between infected and healthy tissues with specificity and sensitivity ex-vivo (Carbary-Ganz et al, 2015).…”

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

“…36 This strategy enables simultaneous longitudinal tracking of morphological (optical coherence tomography) and biochemical (fluorescence) alterations during CRC development and progression. In the carcinogen-treated mice, QDot655 targeted to vascular endothelial growth factor receptor 2 (QD655-VEGFR2) localized to the colon and offered a considerably high contrast between the diseased and healthy tissue with high sensitivity and specificity ex vivo.…”

“…Carbary-Ganz et al 36 developed a technology in which optical coherence tomography/laser-induced fluorescence dual-modality imaging allows for slightly invasive, nondestructive endoscopic visualization of CRC. 36 This strategy enables simultaneous longitudinal tracking of morphological (optical coherence tomography) and biochemical (fluorescence) alterations during CRC development and progression.…”

“…In the carcinogen-treated mice, QDot655 targeted to vascular endothelial growth factor receptor 2 (QD655-VEGFR2) localized to the colon and offered a considerably high contrast between the diseased and healthy tissue with high sensitivity and specificity ex vivo. 36 In another study, researchers developed an exceptional cell-targeted, paramagnetic-fluorescent double-signal molecular nanoprobe (GdDTPA⋅BSA@QDs-PcAb) for in vivo magnetic resonance imaging (MRI) diagnosis and subsequent biopsy of CRC. 37 These multipurpose GdDTPA⋅BSA@QDs-PcAb nanoprobes were synthesized by surface engineering of QDs with DTPA⋅BSA-Gd3 + macromolecule complex under ultrasonication conditions.…”