The main focus of the Optical Molecular Imaging Groningen (OMIG) research group and the research-line Molecular Fluorescence Endoscopy is the translation of novel targeted near-infrared (NIR) optical tracers into the clinic, aiming to improve (pre)malignant lesion detection rates and to gain insight in disease biology in order to evaluate treatment response during endoscopy. The endoscopic research-line embodies the full translation of targeted fluorescent tracers from bench-to-bedside, i.e. from the GMP-development of novel NIR fluorescent tracers, to phase I-II clinical imaging studies.
Molecular Fluorescence Endoscopy potentially enables the detection of disease at an earlier stage, with higher sensitivity and specificity over today’s endoscopic imaging techniques. In patients with colorectal polyps or dysplastic or early cancerous lesions in patients with Barrett’s Esophagus, there currently is a high detection miss-rate. We believe optical molecular imaging using NIR fluorescence can be used as a ‘red-flag’ imaging technique to improve current endoscopic performance in terms of early lesion detection. NIR fluorescent agents targeting certain biomarkers that become overexpressed as the degree of dysplasia progresses, might be used to improve lesion detection rates in these diseases.
Moreover, there may also be a role for molecular fluorescence endoscopy in the evaluation of treatment response in for example patients that are treated with neoadjuvant chemoradiotherapy such as locally advanced esophageal or rectal cancer, but also in inflammatory bowel diseases such as Colitis Ulcerosa or Crohn’s disease.
In the University Medical Center Groningen (UMCG), we have initiated clinical phase-I feasibility studies to determine the safety and feasibility of molecular fluorescence endoscopy for multiple indications. In these studies, also the most optimal dose and the biodistribution of the targeted fluorescent tracers were evaluated. In addition, novel biomarkers that have been identified using methods such as functional genomic mRNA profiling or the Target Selection Criteria (TASC) are being validated ex vivo in order to identify which biomarkers can potentially be used as imaging targets for clinical use. Next to that, we are currently initiating phase-II clinical studies to further validate the results found in phase-I studies and to determine the diagnostic accuracy and clinical impact of molecular fluorescence endoscopy.
In the UMCG and within the OMIG research group, we have the availability of several state-of-the-art imaging instruments that allow both in vivo as well as ex vivo fluorescence imaging. Together with the University of Munich (prof. dr. Vasilis Ntziachristos), a custom-build fiber-based NIR fluorescence endoscopy platform was developed, that was subsequently further developed by SurgVision B.V.. This NIR fluorescence endoscopy platform is capable of real-time fluorescence imaging during endoscopy with simultaneous white-light imaging, using a fiber-based approach. This enables the use of molecular fluorescence endoscopy as a ‘red-flag’ imaging technique, in order to identify areas of interest based on the molecular characteristics of tissue. After identification of areas of interest, in vivo histology can be obtained using confocal laser endomicroscopy (Mauna Kea) combined with near-infrared fluorescence. In addition, fluorescence can be quantified in vivo by correcting for tissue optical properties using a fiber-based multi-diameter single fiber reflectance, single fiber fluorescence spectroscopy device (Dominic Robinson, Erasmus MC, Rotterdam).
Moreover, for translation into the clinic or the ex vivo validation of fluorescent tracers, imaging systems such as the PEARL Imager (LI-COR), the IVIS Spectrum (PerkinElmer) the Odyssey CLx flatbed scanner (LI-COR), the TissueFAXS (TissueGnostics) and a fluorescence microscopy specifically equipped for visualization of fluorescence in the NIR light spectrum are available, among other devices and techniques. Within the UMCG there is an emphasis on a multidisciplinary approach for both clinical as research activities. Together with a validated and standardized ex vivo workflow for the validation of novel fluorescent tracers, this is the base for high-quality research aiming to further improve optical molecular imaging in the clinic.
For specific techniques regarding GMP tracer development, please also visit: ‘Information > Tracer development’ on this website.
About dr. W.B. Nagengast
Wouter Nagengast is trained as a Gastroenterologist and Pharmacist, and currently works in the UMCG as clinical gastroenterologist with a focus on oncology, advanced endoscopic imaging, endoscopic mucosal resection (EMR) and submucosal endoscopic dissection (ESD). He obtained a PhD at the Department of Medical Oncology in 2009. During his PhD he developed several targeted nuclear tracers for molecular imaging and validated them in preclinical models and clinical trials. With a fascination for the possibilities of optical imaging, he developed an innovative new endoscopic technology, molecular fluorescence endoscopy (MFE), to detect dysplasia and perform treatment follow up during endoscopy procedures. Since clinical translation and implementation of this technology require a strong cross-disciplinary team of physicians, chemists, pharmacists, biologists, physicists, and engineers he started, together with Prof. Go van Dam, the research group Optical Molecular Imaging Groningen (www.OMIG.nl). Within OMIG they managed to develop and produce via GMP regulations new fluorescent antibodies and applied them in over 200 patients in clinical trials. Beside fluorescence visualization during endoscopy, OMIG has enabled quantitative fluorescence molecular endoscopy by correcting background tissue optical properties, i.e. absorption and scattering properties of the tissue. By fluorescent labeling of drugs this technology enables quantitative insight in drug distribution in the gastrointestinal tract as recently demonstrated in rectal cancer patients.