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

Scriptie/Masterproef: Doctoral Thesis

Samenvatting

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 responses for approximately 20% of the patients. Despite the positive responses, these treatments remain expensive and potentially have undesirable side-effects on the patients. 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. Our aim is to develop a tracer that would allow whole body PD-L1 visualization by positron emission tomography (PET) imaging. This technique consists of injecting a tracer composed of a targeting molecule that accumulates at the tumor site, and composed of a radionuclide which allows detection by the scanner. In this study, the targeting molecule of interest is a Nanobody. Nanobodies are small antibody fragments found in Camelidae (e.g. Lamas, alpacas) and a Nanobody specifically recognizing PD-L1 has been selected. In this particular project we aim to couple the PD-L1 Nanobody with a radionuclide (Gallium-68 or Fluorine-18) for PET imaging and validate the tracer preclinically. Three different strategies proved efficient to couple the Nanobody with Gallium-68. When tested in preclinical models, we demonstrated that the Nanobody-tracer had excellent properties and could allow imaging of PD-L1 tumors within 80 minutes post injection. We also investigated three different Fluorine-18 labeling techniques which could also be applied to other Nanobodies in general. In view of the clinical demand and in view of its ideal properties, the Gallium-68 labeled PD-L1 Nanobody has the potential to become our next Nanobody in clinical trials.
Datum prijs28 jun 2021
Originele taalEnglish
Prijsuitreikende instantie
  • Vrije Universiteit Brussel
BegeleiderVicky Caveliers (Promotor), Catarina Xavier (Co-promotor), Marleen Keyaerts (Co-promotor), Cécile Perrio (Jury), Ken Kersemans (Jury), Ann Van Eeckhaut (Jury), Cleo Goyvaerts (Jury) & Matthias D'Huyvetter (Jury)

Keywords

  • Nanobodies
  • Immuno Pet Tracer

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