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Single-step Radiosyntheses of '18F-Labeled Click Synthons' from Azide-functionalized Diaryliodonium Salts.

ABSTRACT: Positron emission tomography (PET) is an increasingly important biomedical imaging technique that relies on the development of radiotracers labeled with positron-emitters to achieve biochemical specificity. Fluorine-18 (t1/2 = 109.7 min) is an attractive positron-emitting radiolabel for organic radiotracers, primarily because of its longer half-life and greater availability relative to those for the main alternative, carbon-11 (t1/2 = 20.4 min). Rapid simple methods are sought for labeling prospective PET radiotracers with fluorine-18 from cyclotron-produced aqueous [18F]fluoride ion, which must often be converted first into a suitably reactive labeling synthon for use in a subsequent labelling reaction. Use of 18F-labeled synthons in 'click chemistry' attracts increasing attention for labeling PE Tradiotracers. Here we describe rapid single-step radiosyntheses of azido- or azidomethyl-bearing [18F]fluoroarenes from the reactions of diaryliodonium salts with no-carrier-added [18F]fluoride ion within a microfluidic apparatus to provide previously poorly accessible 18F-labeled click synthons in radiochemical yields of 15% for [18F]4-fluorophenyl azide and about 40% for each of the [18F](azidomethyl)-fluorobenzenes. The radiosyntheses of the latter synthons was possible under 'wet conditions', so obviating the need to dry the cyclotron-produced [18F]fluoride ion and greatly enhancing the practicality of the method.

SUBMITTER: Joong-Hyun C

PROVIDER: S-EPMC3922306 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Single-step Radiosyntheses of '18F-Labeled Click Synthons' from Azide-functionalized Diaryliodonium Salts.

Joong-Hyun Chun C Pike Victor W VW

European journal of organic chemistry 20120801 24

Positron emission tomography (PET) is an increasingly important biomedical imaging technique that relies on the development of radiotracers labeled with positron-emitters to achieve biochemical specificity. Fluorine-18 (t1/2 = 109.7 min) is an attractive positron-emitting radiolabel for organic radiotracers, primarily because of its longer half-life and greater availability relative to those for the main alternative, carbon-11 (t1/2 = 20.4 min). Rapid simple m ...[more]

PMID: 24532989

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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

Single-step Radiosyntheses of '18F-Labeled Click Synthons' from Azide-functionalized Diaryliodonium Salts.

Publications

Single-step Radiosyntheses of '<sup>18</sup>F-Labeled Click Synthons' from Azide-functionalized Diaryliodonium Salts.

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