In order to fluorescently label your compound of interest, either for imaging purposes or drug development, we offer the full package for GLP and GMP fluorescent labelling using various (near-infrared) fluorophores. As part of the diagnostic window in fluorescent imaging, we use predominantly near-infrared fluorphores such as IRDye800CW or equivalents in the same wavelength. All labelling procedures adhere to GLP / GMP guidelines within our GMP unit, accompanied by analytical reports, stability tests etc.
In the beginning of our first clinical experience we have used small peptide conjugated to a fluorophore, such as folate coupled to fluoresceine isothiocyanate in patients with ovarian cancer with our collaborators at Purdue University. Since then, we have shifted gears towards labelling targeting moieties with a near-infrared (NIR) fluorophore (IRDye800CW) and based on our vast experience of radionuclide labelling (89Zirconium) of therapeutic antibodies, e.g. bevacizumab (Avastin©), trastuzumab (Herceptin©), and cetuximab (Erbitux©), since 2011 we produce bevacizumab-IRdye800CW, trastuzumab-IRDye800Cw and cetuximab-IRdye800CW in our GMP facility.
Due to our longstanding experience in labelling drugs for clinical evaluation through our GMP (biologicals) facility, we are also able to produce tumor-specific nanobodies, i.e. HER2/neu-IRDye800CW and carbonic anhydrase (CAIX)-IRDye800CW in our biologicals unit of the GMP facility. All labelling protocols are fully regulatory compliant including full documentation on synthesis, QA/QC and stability testing, release etc. Besides labelling with fluorophores at our GMP facility with the support of our (nuclear) biochemists, we also have shown the capacity to label antibodies or nanobodies with a photosensitizer such as IRDye700DX for photoimmunotherapy purposes. Not only can such compounds be used as an imaging agent, but also deliver data on the tumor (micro-) distribution of the fluorescent compound and be applied as a true theranostic agent. The distribution of these compounds can be easily tracked on a mesoscopic scale, and in conjunction with standard histopathology and dedicated immunohistochemistry, this delivers unprecedented information on the fate of the labelled compound in relation to the disease process.
In order to deliver the necessary standardization in fluorescent tracer development, translation and evaluation, and part of a regulatory approval, we have developed novel Standard Operating Procedures for training surgeons, pathologists and gastroenterologists in the interpretation and qualification of fluorescence within the UMCG skills center. Likewise, the Standard of Care is continuously evaluated by inter- and intraobserver agreement studies prior, during and after the clinical studies. For ex vivo validation of tracer distribution in specimen, a so-called fSTREAM and Multiplexed Advanced Pathology Imaging (MAPI) SOP is in place to guarantee full standardization in the execution of preclinical and clinical studies.