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- Title
Sulfonyl Fluoride-Based Prosthetic Compounds as Potential <sup>18</sup>F Labelling Agents.
- Authors
Inkster, James A. H.; Liu, Kate; Ait-Mohand, Samia; Schaffer, Paul; Guérin, Brigitte; Ruth, Thomas J.; Storr, Tim
- Abstract
Nucleophilic incorporation of [18F]F− under aqueous conditions holds several advantages in radiopharmaceutical development, especially with the advent of complex biological pharmacophores. Sulfonyl fluorides can be prepared in water at room temperature, yet they have not been assayed as a potential means to 18F-labelled biomarkers for PET chemistry. We developed a general route to prepare bifunctional 4-formyl-, 3-formyl-, 4-maleimido- and 4-oxylalkynl-arylsulfonyl [18F]fluorides from their sulfonyl chloride analogues in 1:1 mixtures of acetonitrile, THF, or tBuOH and Cs[18F]F/Cs2CO3(aq.) in a reaction time of 15 min at room temperature. With the exception of 4- N-maleimide-benzenesulfonyl fluoride ( 3), pyridine could be used to simplify radiotracer purification by selectively degrading the precursor without significantly affecting observed yields. The addition of pyridine at the start of [18F]fluorination (1:1:0.8 tBuOH/Cs2CO3(aq.)/pyridine) did not negatively affect yields of 3-formyl-2,4,6-trimethylbenzenesulfonyl [18F]fluoride ( 2) and dramatically improved the yields of 4-(prop-2-ynyloxy)benzenesulfonyl [18F]fluoride ( 4). The N-arylsulfonyl-4-dimethylaminopyridinium derivative of 4 ( 14) can be prepared and incorporates 18F efficiently in solutions of 100 % aqueous Cs2CO3 (10 mg mL−1). As proof-of-principle, [18F] 2 was synthesised in a preparative fashion [88(±8) % decay corrected ( n=6) from start-of-synthesis] and used to radioactively label an oxyamino-modified bombesin(6-14) analogue [35(±6) % decay corrected ( n=4) from start-of-synthesis]. Total preparation time was 105-109 min from start-of-synthesis. Although the 18F-peptide exhibited evidence of proteolytic defluorination and modification, our study is the first step in developing an aqueous, room temperature 18F labelling strategy.
- Publication
Chemistry - A European Journal, 2012, Vol 18, Issue 35, p11079
- ISSN
0947-6539
- Publication type
Article
- DOI
10.1002/chem.201103450