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Synthesis and preliminary radiopharmacological characterisation of an 11 C‐labelled azadipeptide nitrile as potential PET tracer for imaging of cysteine cathepsins
Author(s) -
Laube Markus,
Frizler Maxim,
Wodtke Robert,
Neuber Christin,
Belter Birgit,
Kniess Torsten,
Bachmann Michael,
Gütschow Michael,
Pietzsch Jens,
Löser Reik
Publication year - 2019
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.3729
Subject(s) - chemistry , nitrile , cathepsin , methyl iodide , cysteine , radiochemistry , in vivo , imaging agent , stereochemistry , biochemistry , organic chemistry , microbiology and biotechnology , biology , enzyme
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 [ 11 C]methyl iodide starting from cyclotron‐produced [ 11 C]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 nonradioactive 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 18 F‐fluoroethylated analogue and suggests the limited suitability of azadipeptide nitriles for the imaging of tumour‐associated cysteine cathepsins despite target‐mediated uptake is evidenced.