Dataset Information

An Unconventional Mechanistic Insight into SCF3 Formation from Difluorocarbene: Preparation of 18 F-Labeled ?-SCF3 Carbonyl Compounds.

ABSTRACT: Trifluoromethylthiolation by sulfuration of difluorocarbene with elemental sulfur is described for the first time, which overrides long-standing trifluoromethyl anion-based theory. Mechanistic elucidation reveals an unprecedented chemical process for the formation of thiocarbonyl fluoride and also enables transition-metal-mediated trifluoromethylthiolation and [18 F]trifluoromethylthiolation of ?-bromo carbonyl compounds with broad substrate scope and compatibility.

SUBMITTER: Zheng J

PROVIDER: S-EPMC5582945 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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An Unconventional Mechanistic Insight into SCF3 Formation from Difluorocarbene: Preparation of 18 F-Labeled α-SCF3 Carbonyl Compounds.

Zheng Jian J Cheng Ran R Lin Jin-Hong JH Yu Dong-Hai DH Ma Longle L Jia Lina L Zhang Lan L Wang Lu L Xiao Ji-Chang JC Liang Steven H SH

Angewandte Chemie (International ed. in English) 20170214 12

Trifluoromethylthiolation by sulfuration of difluorocarbene with elemental sulfur is described for the first time, which overrides long-standing trifluoromethyl anion-based theory. Mechanistic elucidation reveals an unprecedented chemical process for the formation of thiocarbonyl fluoride and also enables transition-metal-mediated trifluoromethylthiolation and [18 F]trifluoromethylthiolation of α-bromo carbonyl compounds with broad substrate scope and compatibility. ...[more]

PMID: 28194833

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Project description:BackgroundCancer-associated fibroblasts are found in the stroma of epithelial tumors. They are characterized by overexpression of the fibroblast activation protein (FAP), a serine protease which was already proven as attractive target for chelator-based theranostics. Unfortunately, the value of gallium-68 labeled tracers is limited by their batch size and the short nuclide half-life. To overcome this drawback, radiolabeling with aluminum fluoride complexes and 6-fluoronicotinamide derivatives of the longer-lived nuclide fluorine-18 was established. The novel compounds were tested for their FAP-specific binding affinity. Uptake and binding competition were studied in vitro using FAP expressing HT-1080 cells. HEK cells transfected with the closely related dipeptidyl peptidase-4 (HEK-CD26) were used as negative control. Small animal positron emission tomography imaging and biodistribution experiments were performed in HT-1080-FAP xenografted nude mice. [18F]AlF-FAPI-74 was selected for PET/CT imaging in a non-small cell lung cancer (NSCLC) patient.ResultsIn vitro, 18F-labeled FAPI-derivatives demonstrated high affinity (EC50 = < 1 nm to 4.2 nm) and binding of up to 80% to the FAP-expressing HT1080 cells while no binding to HEK-CD26 cells was observed. While small animal PET imaging revealed unfavorable biliary excretion of most of the 18F-labeled compounds, the NOTA bearing compounds [18F]AlF-FAPI-74 and -75 achieved good tumor-to-background ratios, as a result of their preferred renal excretion. These two compounds showed the highest tumor accumulation in PET imaging. The organ distribution values of [18F]AlF-FAPI-74 were in accordance with the small animal PET imaging results. Due to its less complex synthesis, fast clearance and low background values, [18F]AlF-FAPI-74 was chosen for clinical imaging. PET/CT of a patient with metastasized non-small cell lung cancer (NSCLC), enabled visualization of the primary tumor and its metastases at the hepatic portal and in several bones. This was accompanied by a rapid clearance from the blood pool and low background in healthy organs.Conclusion[18F]AlF-labeled FAPI derivatives represent powerful tracers for PET. Owing to an excellent performance in PET imaging, FAPI-74 can be regarded as a promising precursor for [18F]AlF-based FAP-imaging.

Dataset Information

An Unconventional Mechanistic Insight into SCF3 Formation from Difluorocarbene: Preparation of 18 F-Labeled ?-SCF3 Carbonyl Compounds.

Publications

An Unconventional Mechanistic Insight into SCF<sub>3</sub> Formation from Difluorocarbene: Preparation of <sup>18</sup> F-Labeled α-SCF<sub>3</sub> Carbonyl Compounds.

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