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

• Published in: Bioorganic & medicinal chemistry 2006-12, Vol.14 (24), p.8599-8607
• Main Authors: Wang, Min, Gao, Mingzhang, Mock, Bruce H., Miller, Kathy D., Sledge, George W., Hutchins, Gary D., Zheng, Qi-Huang
• Format: Article
• Language: English
• Subjects: Animals; Benzothiazoles - chemical synthesis; Benzothiazoles - chemistry; Biological and medical sciences; Cancer imaging; Carbon Radioisotopes; Carbon-11; Contrast media. Radiopharmaceuticals; Fluorinated 2-arylbenzothiazoles; Humans; Medical sciences; Neoplasms - diagnostic imaging; Pharmacology. Drug treatments; Positron emission tomography (PET); Positron-Emission Tomography; Radiopharmaceuticals - chemical synthesis; Radiopharmaceuticals - chemistry; Tomography, Emission-Computed; Tyrosine kinase
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2006.08.026

Synthesis of carbon-11 labeled fluorinated 2-arylbenzothiazoles as novel potential PET cancer imaging agents is reported. 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 H 2/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.