Development of a novel chemoenzymatic technology to generate radiofluorinated PET tracers

Project Details

Description

Nanobodies (Nbs) are antibody-fragments that make interesting tools
for Positron Emission Tomography (PET) imaging. A previouslydeveloped Nb targeting Programmed Death Ligand 1 (PD-L1)
displays promising properties as a PET tracer for stratification and
prediction of treatment outcome of patients potentially eligible for
immune-therapy. Fluorine-18 (18F) is the most ideal PET
radionuclide for clinical application as it can be produced in high
activity batches, has an appropriate half-life and enables imaging
with good resolution. However, no clinical trials have yet been
conducted with 18F-labeled Nbs due to the harsh conditions required
for direct radiofluorination. Current techniques in preclinical
development circumvent this issue by time-consuming two-step
protocols. With the aim of facilitating radiofluorination of Nbs,
enzymes are of interest, as they allow for radiolabeling in aqueous
media under mild conditions, preserving the Nbs’ integrity. Here, we
intent to utilize the novel ligase Butelase, with kinetics unmatched by
other ligases, as an efficient radiolabeling tool for Nbs. We aim to
investigate the enzyme’s bioconjugation potential in indirect and
direct radiolabeling procedures. Our goal is to optimize 'one-pot'
radiofluorination, during which the Butelase catalyzes the coupling
between the Nb and a 18F-labeled substrate. Another goal is full
automation of this process, enabling user-friendly implementation of
radiofluorinated PET tracers in the clinic.
AcronymFWOSB114
StatusActive
Effective start/end date1/11/2131/10/26

Keywords

  • Nanobody
  • Butelase
  • radiofluorination

Flemish discipline codes in use since 2023

  • Cancer diagnosis
  • Medical molecular engineering of nucleic acids and proteins
  • Radiopharmacy
  • Applied immunology
  • Nuclear imaging

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