"Radiolabeling Strategies of Nanobodies: Development of an Immuno-PET Tracer for PD-L1 Imaging"

Cancer cells are able to escape from the immune system and further proliferate by expressing a protein called “PD-L1”. Treatments exist to block PD-L1, but they only show positive outcomes in a subset of patients. Despite the positive responses, these treatments remain expensive and potentially have undesirable side-effects. Therefore, there is a need for new tools to visualize if the host’s cancer cells are expressing PD-L1, to help doctors select patients who could benefit from the treatments.
 
One strategy to visualize whole-body PD-L1 is by positron emission tomography (PET) imaging. This technique consists of injecting a tracer composed of a targeting molecule that accumulates at the tumor lesion, and a radionuclide which allows detection by the scanner. Nanobodies are recombinantly isolated antigen-binding domains of camelid heavy-chain-only antibodies. They have proven to be promising targeting agents for PET imaging because of their ease of production, stability and fast clearance through the kidneys.
 
In this thesis, we developed Nanobody-based radiopharmaceutical analogues for PET imaging of PD-L1 expression. The obtained results provide grounds for the subsequent selection of radiochemical and radiopharmaceutical procedures in the clinical translation of the PD-L1 Nanobody. More generally, the work performed in the framework of this thesis contributes to any future translational approaches of Nanobodies for PET imaging.