Poster Presentation Royal Australian Chemical Institute National Congress 2026

Synthesis and Radiolabelling of a [64Cu][Cu(NOTA)] Nanobody for Fibroblast Activation Protein Targeting (#125)

Sophie Stevens 1 , Stacey Rudd 1 , Rachel Maclean 2 , Samuel Graf 2 , Mark Frazzetto 2 , Gregory Santamaria 2 , Jasdave Chahal 3 , Paul Donnelly 3
  1. School of Chemistry & Bio21 Molecular Science and Biotechnology Institute, Melbourne, Victoria, Australia
  2. Cyclotek, North Melbourne
  3. Revela Bio, LLC, Cambridge

Developing radiopharmaceuticals by incorporating biomolecules is a powerful tool for the targeted delivery of radioisotopes. The positron-emitting radionuclide copper-64 can be complexed with the NOTA chelator to generate tracers for positron emission tomography (PET) imaging and disease diagnosis. Fibroblast activation protein (FAP) is overexpressed on cancer-associated fibroblasts, emerging as a target for PET imaging and radiopharmaceutical therapy. Nanobodies, single-domain antibodies derived from camelids, possess high affinity, small size, and excellent tissue penetration, making them ideal targeting biomolecules. Here, we use sortase-mediated enzymatic conjugation in combination with click chemistry. These techniques enable site-specific attachment of a chelator and controlled incorporation of a PEG pharmacokinetic modulator to a FAP-targeting nanobody. Following this, the tracer can be radiolabelled with copper-64 for evaluation in a FAP tumour mouse model. This strategy presents potential to generate FAP-targeted PET imaging agents.