[18F]Difluorocarbene for positron emission tomography

Abstract

The advent of total-body Positron EmissionTomography (PET) has vastly broadened the range of research and clinical applications of this powerful molecular imaging technology. 1 Such possibilities have accelerated progress in 18 F-radiochemistry with numerous methods available to 18 F-label (hetero)arenes and alkanes. 2 However, access to 18 F-difluoromethylated molecules in high molar activity (Am) is largely an unsolved problem, despite the indispensability of the difluoromethyl group for pharmaceutical drug discovery. 3 We report herein a general solution by introducing carbene chemistry to the field of nuclear imaging with a [ 18 F]difluorocarbene reagent capable of a myriad of 18 F-difluoromethylation processes. In contrast to the tens of known difluorocarbene reagents, this 18 F-reagent is carefully designed for facile accessibility, high molar activity and versatility. The issue of Am is solved using an assay examining the likelihood of isotopic dilution upon variation of the electronics of the difluorocarbene precursor. Versatility is demonstrated with multiple [ 18 F]difluorocarbene based reactions including O-H, S-H and N-H insertions, and cross-couplings that harness the reactivity of ubiquitous functional groups such as (thio)phenols, N-heteroarenes, and aryl boronic acids that are easy to install. Impact is illustrated with the labelling of highly complex and functionalised biologically relevant molecules and radiotracers.

Emerging Biomaterials Imaging Antitumor Immune Response

“…Molecular tracking technology in nuclear medicine provides an effective method for the early diagnosis and prognosis of tumors. [51] Specific antibodies labeled with radioactive molecular probes can be used to evaluate the expression levels of PD-1 and PD-L1, which are useful for screening patients with effective immune responses and serve as an important alternative to the use of pathological slices in tumors. [52,53] CT remains the gold standard for lung cancer detection, but it has poor specificity and may cause complications.…”

Recent Advances in 18F-Labeled Amino Acids Synthesis and Application

“…Direct radiofluorination on AAs bearing electron-rich arenes, such as Phe, Tyr, and tryptophan (Trp), is a difficult task when traditional S N 2 or S N Ar reactions are used. To solve this problem, several new fluorine-18 radiochemical methodologies have been reported [ 28 , 29 , 30 , 31 ]. As transition-metal catalysis can accelerate radiofluorination reaction rates and enhance selectivity and reactivity, transition metal-catalyzed methodologies have emerged as an attractive technique with which to fluorinate arenes with nucleophilic fluoride sources [ 32 , 33 ].…”

Highlight selection of radiochemistry and radiopharmacy developments by editorial board

“…Recently, a new [ 18 F]difluorocarbene reagent [ 18 F]1 (Fig. 3 A) has been reported available for versatile 18 F-difluoromethylation as an alternative to 11 C-methylation (Sap et al 2022 ). Using the [ 18 F]difluorocarbene reagent, they prepared 47 18 F-difluoromethylated derivatives, which include 19 bioactive compounds, from (thio)phenols and N-heterocycles (Fig.…”