As one of the most advanced technologies currently available for studyingin vivomolecular interactions, positron emission tomography (PET) is a functional imaging technique that can produce a three-dimensional image of functional processes in the body. It has served as a powerful medical tool and has been heavily used in clinical oncology, clinical diagnosis of certain diffuse brain diseases, and so on. Since PET imaging requires the preparation of a positron-emitting radiolabelled probe or radiotracer, the selection of a proper positron-emitting isotope is quite important. Fluorine-18 (¹⁸F) has proved to be a nice choice due to its relatively long half-life of 109.7 min, high-yielding production and high specific activity, importance of fluorine substitution as isotopologue in drug discovery, and extensive clinical use of [¹⁸F]FDG (2-[18F]fluoro-2-deoxy-D-glucose). Therefore, significant efforts have been devoted to the exploration of novel and efficient methodologies for¹⁸F-incorporation into small or biological molecules.

Trifluoromethylthio group (CF₃S) is a valuable pharmacophore in medicinal chemistry and drug discovery, but the formation of [¹⁸F]CF₃S moiety has never been realized and thus remains a significant challenge. Given that half-life of¹⁸F is short and [¹⁸F]F^–is a good¹⁸F source, it can be speculated that the best protocol for the installation of [¹⁸F]CF₃S functionality is a fast reaction involving the use of [¹⁸F]F^–. Although outstanding accomplishments have been recently made for the incorporation of CF₃S group via non-radioactive trifluoromethylthiolation methods, the CF₃S scaffold are derived from CF₃S- or CF₃-containing reagents without the involvement of external fluoride, which makes it not applicable or difficult for translation into¹⁸F-radiolabeling.

We have developed an efficient method for trifluoromethylthiolation of aliphatic electrophiles based on the reaction between difluorocarbene, elemental sulfur and fluoride ion (eq. 1). This strategy has been successfully applied to the first¹⁸F-labelled [¹⁸F]trifluoromethylthiolation reaction (eq. 2). The present discovery is also significant given the short reaction time (≤1 min) and operational simplicity for [¹⁸F]trifluoromethylthiolation, which is ideal for short-lived radionuclide¹⁸F and automated radiosynthesis. This approach also requires no participation of transition metals and thus eliminates the risk of introducing toxic metals into final formulation for injection. All of these advantages make this method suitable for the preparation of [¹⁸F]CF₃S-labeled pharmaceuticals and subsequent PET imaging studies.

Publication

Difluorocarbene-Derived Trifluoromethylthiolationand [18 F]Trifluoromethylthiolation of Aliphatic Electrophiles.
Zheng J, Wang L, Lin JH, Xiao JC, Liang SH
Angew Chem Int Ed Engl. 2015 Sep 21

Read offline:

Related Articles:

	How PET ameliorates 90-Yttrium therapy in inoperable liver…Increased synthesis of blood vessels and blood supply are essential characteristics of a tumor to secure nutrient delivery and growth. One of the treatment options for inoperable liver cancer (hepatocellular carcinoma,…
	Biodrying. A novel technology to treat organic wastesDifferent reuse pathways for sewage sludge (SS) produced in wastewater treatment plants (WWTPs) and other organic waste exist, such as its direct application as agronomic soil or with a previous…
	Flexible solid-state random lasers emitting radiation in the…The internet of things opened new possibilities relative to the integration of wearable electronics in textile-based devices, allowing the development of new technologies in energy storage and energy harvesting area,…
	In vivo 2-color multiphoton imaging of genetic reporter…Fibroblasts are cells that synthesize collagen and support the maintenance of connective tissue in the skin, tendons, and joints. They maintain a critical role in the immune system’s response to…
	Gas types affect stability of microbubbles and ultrasound…Ultrasound (US) is used for clinical diagnosis and therapy. Microbubbles (MBs) as US-contrast agents are applied to detect micro blood flow or specific lesions. Recently, the combination of MBs and…
	How to choose excitation wavelength for…Light-emitting diodes (LEDs) are fundamental devices for backlights and displays. Nowadays, three different-color epitaxial chips are mainly applied in an RGB pixel: Blue, green, and red LED chips. However, it…