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Development of radiotracers for molecular imaging and detection of tumour-associated matrix-modifying enzymes
1  Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf
2  Faculty of Chemistry and Food Chemistry, School of Science, Technische Universität Dresden
Academic Editor: Maria Emília Sousa (registering DOI)

Remodelling of the extracellular matrix is associated with various disease processes, particularly tumorigenesis. A major part in this process is played by enzymes which catalyse the chemical modification or degradation of matrix proteins, which therefore represent biomolecular targets for both therapeutic intervention as well as for molecular imaging using radiolabelled molecules by positron emission tomography (PET) and single photon emission computed tomography (SPECT). With regards to the latter option of diagnostic targeting, cysteine cathepsins, lysyl oxidases and transglutaminase were taken into focus by us as targets for radiotracer development for functional tumour imaging by PET. While cysteine cathepsins represent prominent tumour-associated matrix-degrading proteases, lysyl oxidases and transglutaminase 2 mediate oxidative and transamidative cross-linking of extracellular proteins, respectively, with various additional intracellular enzymatic functions. After a short introduction into molecular imaging with special emphasis on the importance of PET in drug development and the function of the mentioned enzymes in tumour progression, the pursued strategies for ligand identification, labelling with suitable radionuclides and the results of radiopharmacological characterisation of the tracer compounds will be outlined.

Keywords: activity-based probes; enzyme kinetics; posttranslational modification; proteases; protein cross-linking; radiochemistry; structure-activity relationships
Comments on this paper
Andreas Maurer
Nice presentation, and a particularly good example for covalent targeting of an enzyme without promiscuitive reactivity. Is the metabolism something that you expect to get optimized? Best regards, Andreas