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- Title
Synthesis and preliminary radiopharmacological characterisation of an <sup>11</sup>C‐labelled azadipeptide nitrile as potential PET tracer for imaging of cysteine cathepsins.
- Authors
Laube, Markus; Frizler, Maxim; Wodtke, Robert; Neuber, Christin; Belter, Birgit; Kniess, Torsten; Bachmann, Michael; Gütschow, Michael; Pietzsch, Jens; Löser, Reik
- Abstract
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 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 18F‐fluoroethylated analogue and suggests the limited suitability of azadipeptide nitriles for the imaging of tumour‐associated cysteine cathepsins despite target‐mediated uptake is evidenced.
- Subjects
CYSTEINE; CYANIDES; CATHEPSINS; METHYL iodide; THERAPEUTICS; CELL lines; PHARMACOKINETICS
- Publication
Journal of Labelled Compounds & Radiopharmaceuticals, 2019, Vol 62, Issue 8, p448
- ISSN
0362-4803
- Publication type
Article
- DOI
10.1002/jlcr.3729