¹⁸F‐Labeling of Sensitive Biomolecules for Positron Emission Tomography

Abstract

Positron emission tomography (PET) imaging study of fluorine-18 labeled biomolecules is an emerging and rapidly growing area for preclinical and clinical research. The present review focuses on recent advances in radiochemical methods for incorporating fluorine-18 into biomolecules via ‘direct’ or ‘indirect’ bioconjugation. Recently developed prosthetic groups and pre-targeting strategies, as well as representative examples in 18F-labeling of biomolecules in PET imaging research studies are highlighted.

Chemistry for Positron Emission Tomography: Recent Advances in 11C‐, 18F‐, 13N‐, and 15O‐Labeling Reactions

“…11 C-Labeled trifluoromethyl arenes,i ncluding [ 11 C]flutamide and [ 11 C]lefunomide,e xhibited high RCY and high molar activity (> 200 GBq mmol À1 ). 18 F nuclear reaction in high radioquantity and high specific activity,a nd has ar elatively long half-life (109.8 min) compared to 11 C, which allows for multistep synthesis, extended imaging procedures,a nd off-site use in satellite PET facilities without acyclotron.These favorable characteristics provide as trong stimulus to develop novel 18 F-labeled compounds as well as efficient and translational radiofluorination methods.C omplementary to previous reviews on fluorine-18, [6,[82][83][84][85][86][87][88] we focus on the recent development and breakthroughs in nucleophilic and electrophilic reactions with 18 F( Scheme 13). [77] [ 11 C]COCl 2 is an effective reagent to synthesize 11 C-labeled ureas and carbamates via [ 11 C]isocyanate or [ 11 C]carbamoyl chloride intermediates.A diverse range of ureas and carbamates,including a 11 C-labeled 18-b-glycyrrhetinic acid derivative, [78] [ 11 C]MFTC, [79] [ 11 C]SAR127303, [80] and [ 11 C]MAGL-0519, [81] were efficiently obtained by using [ 11 C]COCl 2 .…”

“…In particular,t he molar activity of 11 C-labeled trifluoromethyl arenes far exceeded their 18 Fc ounterparts (aryl [ 18 F]CF 3 ), thereby providing viable access to radiolabeled mutlifluoromethylated compounds with high molar activity.D iverse methods to prepare [ 11 C]COCl 2 from [ 11 C]CO 2 or [ 11 C]CH 4 have been developed since the 1970s.Among these methods, an efficient automated [ 11 C]COCl 2 synthesis with high RCY (> 80 %) was reported in 2010. [88,89] 3. 18 F nuclear reaction in high radioquantity and high specific activity,a nd has ar elatively long half-life (109.8 min) compared to 11 C, which allows for multistep synthesis, extended imaging procedures,a nd off-site use in satellite PET facilities without acyclotron.These favorable characteristics provide as trong stimulus to develop novel 18 F-labeled compounds as well as efficient and translational radiofluorination methods.C omplementary to previous reviews on fluorine-18, [6,[82][83][84][85][86][87][88] we focus on the recent development and breakthroughs in nucleophilic and electrophilic reactions with 18 F( Scheme 13).…”

“…[176] The 18 F-labeled SCF 3 anion generated in situ from [ 18 F]fluoride,S 8 ,a nd Ph 3 P + CF 2 CO 2 À (PDFA, anovel difluorocarbene reagent [177] )was reported to enable the 18 F-trifluoromethylthiolation of alkyl electrophiles (Scheme 32 B1). [86,88] In 2005, Perrin and coworkers reported the first example of the 18 F-labeling of biomolecules through formation of 18 F À Bb onds (Scheme 33 A). Subsequently,the authors found a-bromocarbonyl compounds could also be converted into a-[ 18 F]SCF 3 carbonyl derivatives (Scheme 32 B2).…”

“…[88] Recently,n ew chelators for the formation of 18 F À Al complexes were developed by Bormans and co-workers to address heatsensitive biomolecules.T he new acyclicp olydentate ligands were less rigid than macrocyclic NOTA,w hich substantially reduced the activation energy for AlÀFcomplexation. [88] Recently,n ew chelators for the formation of 18 F À Al complexes were developed by Bormans and co-workers to address heatsensitive biomolecules.T he new acyclicp olydentate ligands were less rigid than macrocyclic NOTA,w hich substantially reduced the activation energy for AlÀFcomplexation.…”

Hetaryl Bromides Bearing the SO2F Group – Versatile Substrates for Palladium‐Catalyzed C–C Coupling Reactions

“…[2] On the other hand, they undergo selective nucleophilic substitution at the sulfur(VI) electrophilic center under controllable reaction conditions. [5,10] In the field of medicinal chemistry, sulfonyl fluorides have found significant utility as reactive probes in chemical biology and molecular pharmacology since they demonstrate appropriate balance of biocompatibility (including aqueous stability) and protein reactivity as the warheads. [1,3] Heteroaromatic sulfonyl fluorides are known as deoxyfluorination agents; [4,5] in particular, commercially available 2-pyridinesulfonyl fluoride (PyFluor TM , 1) ( Figure 1) is more stable and less prone to the elimination side reaction as compared to other popular deoxyfluorination agents (Deoxo-Fluor, [6] Xtal-Fluor, [7] Fluolead [8] or DAST [9] ).…”