Publications Repository - Helmholtz-Zentrum Dresden-Rossendorf

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Synthesis and preliminary radiopharmacological characterisation of an 11C-labelled azadipeptide nitrile as potential PET tracer for imaging of cysteine cathepsins

Laube, M.; Frizler, M.; Wodtke, R.; Neuber, C.; Belter, B.; Kniess, T.; Bachmann, M.; Gütschow, M.; Pietzsch, J.; Löser, R.


An O-methyltyrosine-containing azadipeptide nitrile was synthesised and investigated for its inhibitory activity towards cathepsins L, S, K and B. Labelling with carbon-11 was accomplished by reaction of the corresponding phenolic precursor with [11C]methyl iodide starting from cyclotron-produced [11C]methane. Radiopharmacological evaluation of the resulting radiotracer in a mouse xenograft model derived from a mammary tumour cell line by small animal PET imaging indicates tumour targeting with complex pharmacokinetics. Radiotracer uptake in the tumour region was considerably lower under treatment with the non-radioactive reference compound and the epoxide-based irreversible cysteine cathepsin inhibitor E64. The in vivo behaviour observed for this radiotracer largely confirms that of the corresponding 18F-fluoroethylated analogue and suggests the limited suitability of azadipeptide nitriles for the imaging of tumour-associated cysteine cathepsins

Keywords: pharmacokinetics; cysteine cathepsins; tumour-associated enzymes; molecular imaging; enzyme inhibitors