Synthesis of carbon-11 labeled fluorinated 2-arylbenzothiazoles as novel potential PET cancer imaging agents

Fluorinated 2-arylbenzothiazoles are new potential antitumor drugs, which show potent and selective inhibitory activity against breast, lung, and colon cancer cell lines. Carbon-11 labeled fluorinated 2-arylbenzothiazoles may serve as novel probes for positron emission tomography (PET) to image tyrosine kinase in cancers. The preparation of 4-fluorinated 2-arylbenzothiazoles 4-fluoro-2-(3-benzloxy-4-methoxyphenyl)benzothiazole (6a) and 4-fluoro-2-(3,4-dimethoxyphenyl)benzothiazole (6b) was achieved by a modification of Jacobson thioanilide radical cyclization chemistry. Hydrogenolytic cleavage of the benzyl ether group of compound 6a using H₂/Pd–C provided the precursor 4-fluoro-2-(3-hydroxy-4-methoxyphenyl)benzothiazole (7) for radiolabeling. Synthesis of radiolabeling precursors and the reference standards 5- and 6-fluorinated arylbenzothiazoles (11c–n) was achieved via the reaction of o-aminothiophenol disulfides with substituted benzaldehydes under reducing conditions. The target radiotracers carbon-11 labeled 4-, 5-, and 6-fluorinated arylbenzothiazoles (3-[¹¹C]6b, 4-[¹¹C]11c, 3-[¹¹C]11c, 5-[¹¹C]11f, 4-[¹¹C]11f, 4-[¹¹C]11i, 3-[¹¹C]11i, 5-[¹¹C]11l, and 4-[¹¹C]11l) were prepared by O-[¹¹C]methylation of the phenolic hydroxyl precursors (7, 11d, 11e, 11g, 11h, 11j, 11k, 11m, and 11n) with [¹¹C]methyl triflate and isolated by solid-phase extraction (SPE) purification in 30–55% radiochemical yields.