With their outstanding target selectivity and excellent binding affinity, radiolabeled full-sized antibodies are highly valuable tools for investigating and validating novel biomarkers markers as potential targets for imaging approaches. In our group, we use site-specifically radiolabeled und thus fully immune-reactive antibodies to identify suitable cell surface markers on immune cells in the TME that may provide relevant information on immune cell infiltration and activation. However, since full-sized antibodies display unfavorable pharmacokinetics for clinical imaging applications, we strive to translate our findings directly to smaller antibody-based protein formats (e.g. diabodies) with improved clearance kinetics. By combining such innovative protein formats (developed by S. Dunn, Hi-TIDe: LAbCore immunoglobulin discovery and engineering) with straightforward radiolabeling approaches we aim at ultimately providing an adaptable, readily expandable PET imaging platform for different targets in the TME.

Since small synthetic peptides represent exceptionally versatile molecular targeting vectors, combining high affinities for their molecular target with fast, tunable pharmacokinetics, most of our tracer development efforts are directed towards novel peptide-based tracers. The molecular targets we aim to address with these peptidic radiopharmaceuticals encompass immune checkpoints, different chemokine receptors and other immune-cell population specific cell-surface markers with high relevance in the TME. In those different projects, we are particularly interested in tackling the challenge of visualizing small numbers of specific immune cells with (oftentimes) relatively low target expression in the TME – which requires particularly high binding affinity and specifically adapted tracer pharmacokinetics.