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Science to Practice |
Department of Diagnostic Radiology,
Philipps University Marburg, University Hospital
Giessen and Marburg
Baldinger Strasse
35033 Marburg, Germany
heverhag@mailer.uni-marburg.de
SUMMARY
Alencar et al (1) have demonstrated in mice that the combination of white light endoscopy and near-infrared (NIR) endoscopy using smart imaging probes and fiberoptic microcatheters can improve the detection of small colorectal adenocarcinomas.
THE SETTING
Although the commonly applied screening tool of endoscopy is able to reduce the rate of deaths from colorectal cancer, it also misses nearly a quarter of the lesions present (2). "Smart" imaging probes, activated by proteases, have been shown to be able to specifically demonstrate adenomatous polyps in the small bowel ex vivo (3). In this issue of Radiology, Alencar et al (1) describe how the use of the combination of an NIR optical smart imaging probe and fiberoptic microcatheters improves the detection of even small adenocarcinomas in the colon in a mouse model.
THE SCIENCE
Smart imaging probes are activated by specific properties of a tumor. For NIR fluorescent probes, the fluorescent emission is inhibited by the proximity of the fluorochromes to each other. Some biologically relevant proteases capable of cleaving lysine-lysine bonds are able to activate these probes, resulting in a signal intensity increase of 15–30 times (4). Especially, cathepsin B overexpressed by human colonic neoplasms has shown to be a potent activator of this probe (5). The probe emits NIR light at a wavelength of about 700 nm. A small imaging catheter (outer diameter, 0.8 mm) that can be inserted into a mouse colon is able to transmit light from the colon to a camera placed outside the body (6). With this approach, white light images and NIR images can be acquired simultaneously.
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Further work is needed to evaluate this technique's performance in naturally occurring tumors that will show a more diverse genetic distribution than the single cell line evaluated by Alencar et al (1). Moreover, the accuracy of the method has to be evaluated in the setting of other disease, such as polyposis syndromes or inflammatory bowel disease, being present.
THE PRACTICE
Clinical use:
Endoscopy as a routine screening tool for colorectal cancer already allows detection of early colonic abnormalities. However, a rate of missed lesions of up to 25% makes improvements in the technique mandatory. The work presented by Alencar et al (1) shows that NIR imaging with smart imaging probes and microcatheters may very well be feasible in a clinical setting. The microcatheters used here can easily fit into the working channel of clinical endoscopes and can be used as an adjunct to conventional optical endoscopy (6). The high specificity of NIR probes, in addition to their high target-to-background signal intensity ratios, can enable detection of very small or flat lesions that are usually not seen with white light endoscopy. Therefore, the combination of white light colonoscopy with NIR fluorescent endoscopy is now an important step closer to clinical reality.
Future opportunities and challenges:
Aside from colonic investigations, a new dual approach of a white light and NIR imaging endoscopic device could improve cancer detection in the entire gastrointestinal tract. Moreover, it has the potential to improve tumor localization during minimally invasive surgery. Human safety issues related to the use of smart imaging probes have to be addressed in clinical trials. In addition, dual-approach hardware containing both a white light and an NIR imaging endoscope has to be developed for human applications. Moreover, as outlined by Alencar et al (1), the specificity of the methods in regard to other disease (eg, polyposis syndromes, inflammatory bowel disease) needs evaluation. As for drug development, extensive and rigorous clinical trials will be required to establish the role of this dual-modality smart imaging probe approach for the future of gastrointestinal cancer detection.
FOOTNOTES
See also the article by Alencar et al in this issue.
References
Related Article
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