A consortium of five European partners, among which Tagworks Pharmaceuticals, has secured a €6 million grant from the EU Horizon2020 program for their research action entitled In Vivo Click PET Imaging Agents: Improving clinical companion diagnostics – Click-It. Coordinator of the Click-It consortium is the University of Copenhagen and next to Tagworks, the other partners are the Technical University of Vienna, the Austrian Institute of Technology and the Johannes Gutenberg University in Mainz (Germany).
Companion diagnostics are crucial for drug development and disease management with regard to patient selection, therapy planning and monitoring. Antibodies have been proven to be optimal disease-targeting and -modulating agents. However, to date, nuclear imaging of antibodies has been limited to the use of long-lived isotopes to be compatible with their slow pharmacokinetics. Major drawbacks include high radiation doses, precluding routine and repeated companion imaging procedures.
The Click-It consortium aims to circumvent this issue by using a pretargeting approach, which centers on the administration and target binding of a tagged antibody followed by administration and binding of a small, fast-clearing, short-lived radiolabeled probe to the tag of the antibody. This results in lower absorbed radiation doses and in a boost in target-blood ratios, which in turn leads to a superior imaging contrast. PET scan snapshots at multiple time-points provide long-term imaging information by applying short-lived nuclides. So far, only the fastest click reaction, the tetrazine ligation, has demonstrated potential in clinically relevant conditions. Tagworks has shown in SPECT imaging studies that this click reaction can be applied for the imaging of non-internalizing antibodies in vivo. This project aims at expanding the scope of click-pretargeted imaging to 18F-labeled tetrazines for PET imaging and to internalizing antibodies.