Rapport final
Immuno-PET imaging using the human anti PD-L1 Nanobody: development of radiolabelling techniques - Bridoux Jessica
Some cancer cells can evade the anti-tumor immune response by expressing a protein called PD-L1. Treatments blocking PD-L1 are available but approximately 20% of the patients show positive responses. We aim to develop a diagnostic tool to detect if cancer cells are expressing PD-L1, which will help select patients who can benefit from the existing treatments. Nanobodies are small tracers used to detect cancer cells. We have previously developed a Nanobody able to specifically recognize PD-L1. To be able to perform positron emission tomography (PET) imaging, our goal is to attach a radioactive label to the Nanobody. Two radionuclides are of interest for this purpose: gallium-68 (68Ga) and fluorine-18 (18F). For 68Ga-labeling, the Nanobody was modified with a molecule containing a “chelator” that entraps 68Ga within 10 minutes in aqueous solution. Two main
approaches were investigated and compared to attach the chelator. The first approach is referred as “random” because the chelator was attach onto the Nanobody’s structure at various places. The second approach is referred as “site-specific” because an enzyme was used to control the site of attachment of the chelator onto the Nanobody. We demonstrated that both approaches were valid for 68Ga-labeling of this Nanobody. 18F-labeling is more complex because it occurs in harsh conditions (high temperature, solvents) which are not compatible with our Nanobody. In this project we investigated small molecules already containing 18F which can be coupled in mild conditions onto the Nanobody. The hPD-L1 Nanobody should soon undergo clinical trials for evaluation as a PETtracer.