Preparation of a novel radiotracer targeting the EphB4 receptor via radiofluorination using spiro azetidinium salts as precursor. (2nd August 2017)

• Record Type: Journal Article
• Authors: Wiemer, Jens; Steinbach, Jörg; Pietzsch, Jens; Mamat, Constantin
• Is Part Of: Journal of labelled compounds & radiopharmaceuticals. Volume 60:Number 10(2017)
• Page Start: 489
• Page End: 498
• Publication Date: 2017-08-02
• Subjects: EphB4 ligand -- spiro salts -- N‐(pyrimidinyl)indazolamine; Tracers (Chemistry) -- Periodicals; Radiopharmaceuticals -- Periodicals; 615.8424
• DOI: 10.1002/jlcr.3526
• Languages: English
• ISSNs: 0362-4803

Abstract

Abstract : The visualization of Eph receptors, which are overexpressed in various tumor entities, using selective small molecule Eph inhibitors by means of positron emission tomography is a promising approach for tumor imaging. N ‐(Pyrimidinyl)indazolamines represent a class of compounds, which are known to have high affinity especially for the EphB4 receptor. Radiofluorination of these compounds could provide a highly specific imaging agent and was investigated using a classical nucleophilic introduction of [ 18 F]fluoride as well as a less common nucleophilic ring‐opening reaction of azetidinium salts. In the past, radiofluorinations using azetidinium precursors were demonstrated to result in high radiochemical yields in short periods. For this purpose, an azetidinium precursor based on the N ‐(pyrimidinyl)indazolamine lead compound was developed, and radiofluorination was successfully accomplished. The respective [ 18 F]radiotracer was quickly prepared with high radiochemical purity >97% and in a radiochemical yield of 34%. Abstract : The synthesis and 18 F‐labeling of N‐(pyrimidinyl)indazolamines to target the EphB4 receptor are described. Azetidinium salts as precursors were applied for the radiolabeling procedure for a short‐ and high‐yielding introduction of fluorine‐18. The 18 F‐compound was obtained in an RCY of 34% and an RCP of >97%.