AbstractSurgery, in combination with or without chemo and/or radiotherapy, remains the most recommended treatment with curative intent for many localized tumours. Since the prognosis of the patient is greatly impacted by the presence of residual disease, improving the detection of malignant lesions during surgery could be of great benefit. A promising technique to achieve this, is by using fluorescence guidance. Here, fluorescent contrast agents are used intraoperatively to delineate tissues of interest (such as tumors).
In this dissertation, the optimal design of targeted fluorescent tracers based on nanobodies, which are small antigen binding fragments derived from camelid heavy-chain antibodies, was investigated on the preclinical level. Both the properties of the nanobody itself, with regard to their tumor penetrating potential, as well as the effect of the addition of a fluorophore, were evaluated, and a proof of concept image-guided surgery study was performed. Finally, the design of a bimodal nanobody tracer, combining fluorescence and nuclear imaging, was investigated.
This work reveals nanobodies to be very promising candidates for the design of fluorescent and bimodal tracers for surgical guidance. Further developments over the next years must now pave the way for clinical translation, where the true value of these tracers for the patient will be determined.
|Date of Award||13 Nov 2019|
|Supervisor||Sophie Hernot (Promotor), Nick Devoogdt (Co-promotor), Mark Rijpkema (Jury), Hilde de Rooster (Jury), Geert Raes (Jury), Johnny Duerinck (Jury), Philippe De Sutter (Jury) & Ilse Smolders (Jury)|
- residual disease
- hybrid nanobody tracers