Rapid One-Step ¹⁸F-Labeling of Peptides via Heteroaromatic Silicon-Fluoride Acceptors

Abstract

A new class of organosilicon-based radiosynthons, heteroaromatic silicon-fluoride acceptors, namely, HetSiFAs, that readily undergo isotope exchange with dry [18F]­fluoride at room temperature in high radiochemical yield (up to 94%) with good molar activity is reported. Radiofluorination proceeds in a single step in 2 min without high-performance liquid chromatography purification to provide an operationally simple method for 18F-PET tracer production. This method was used to prepare an 18F-labeled commercial tetrapeptide, and positron emission tomography imaging confirmed in vivo stability.

The aluminium-[18F]fluoride revolution: simple radiochemistry with a big impact for radiolabelled biomolecules

“…The radiochemistry can be laborious and as the overall pharmacokinetic (PK) and metabolic profile is influenced by the radiolabelling and linker strategy, an iterative approach to developing suitable radioconjugates may be required which adds complexity. Several late-stage fluorination methods and 18 F-prosthetic group strategies suitable for radiolabelling peptides have been described and some evaluated in the clinic, but none as close in characteristics to the existing 68 Ga radiochemistry as the [ 18 F]AlF method (Allott et al 2020 ; Narayanam et al 2020 ; Kee et al 2020 ; Yuan et al 2018 ; Krishnan et al 2017 ; Cole et al 2014 ). Therefore, if the research experience lies with gallium-68 radiochemistry, the parallels offered by the [ 18 F]AlF method will be a facile adjustment.…”

Synthesis of 18F-Labeled Aryl Fluorosulfates via Nucleophilic Radiofluorination

“…Unlike the previous results, [ 18 F] 28b and [ 18 F] 28b′ were produced from radiofluorination of 28b′ in 8% and 65% RCYs, respectively. The formation of the major radiolabeled product [ 18 F] 28b′ might presumably stem from 19 F/ 18 F isotopic exchange, which has been recently reported. , Aryl fluorosulfates with aldehydic functionalities ([ 18 F] 29b –[ 18 F] 31b ) were obtained in good RCYs from both phenols and their imidazylate derivatives. As prosthetic synthons, functionalized aldehydic aryl fluorosulfates enable the downstream modification of complex molecules.…”

High-Efficiency Production of Radiopharmaceuticals via Droplet Radiochemistry: A Review of Recent Progress

“…28 Notably, the radiochemical yield was similar among all of these approaches. Microdroplet IEX approaches could likely be extended to other tracers based on trifluoroborates, 70,71 aryl fluorosulfate 72 and silicon-fluoride 73,74 with the same benefits.…”