Small Prosthetic Groups in 18 F-Radiochemistry: Useful Auxiliaries for the Design of 18 F-PET Tracers

Site‐Selective, Late‐Stage C−H 18F‐Fluorination on Unprotected Peptides for Positron Emission Tomography Imaging

“…While the impact of prosthetic groups on radiopharmaceutical discovery has been profound, advanced knowledge of structure-activity relationships is required to identify as uitable site for prosthetic group attachment. [8,16] Additionally, this approach can require complex protecting group strategies,m ulti-step syntheses and face challenges with chemo- Figure 1. Prosthetic groups commonly used for 18 F-labelling of peptides and ap rosthetic-group-free 18 F-labelling of Leu-containing peptides.…”

“…selectivity.P rosthetic groups also impact peptide structure, and can negatively affect biological properties that include binding affinity and target specificity,aswell as pharmacokinetic behaviour. [8,17] Thus,anideal scenario would involve the direct and selective 18 F-fluorination of as ingle CÀHb ond in an ative peptide under rapid, mild, and aqueous conditions. While important contributions towards the selective 18 F-and 19 F-fluorination of CÀHbonds in peptides have been made, [18] amine and carboxylic acid protecting groups are mandatory.…”

Comparison of Radioiodine- or Radiobromine-Labeled RGD Peptides between Direct and Indirect Labeling Methods

“…In the case of preparing radiolabeled proteins or peptides, Labeling with radiofluorine normally requires different methods of radioiodine labeling due to distinct physical properties of fluorine. 20) The same methodology for radioiodine labeling could be used for labeling with radiobromine 21) : introduction of a radiobromine molecule at the next position of a hydroxyl group in a phenolic group using an oxidation agent, such as chloramine-T, and introduction of a radiobromine molecule at any position of the benzene ring using a bromodestannylation reaction from corresponding precursor with a trialkylstannyl group, such as […”

Radiolabelled Peptides for Positron Emission Tomography and Endoradiotherapy in Oncology

“…]SFB). Based on the three-step synthesis described by Vaidyanathan and Zalutsky [19], a variety of modifications has been suggested to optimise synthesis and radiopharmaceutical yield [20]). For example, Wüst et al [21] started with the fluorination of 4-N,N,N-trimethylammonium ethyl benzoate followed by the hydrolysis of the ethyl ester and subsequent activation using O-(N-succinimidyl)-N,N,N',N'-tetramethyluronium tetrafluoroborate (TSTU).…”

“…The major obstacle in developing an easy 1-step procedure is found in the reactivity of the activated ester function, which interferes with the fluorination reaction [20]. Regardless of that, some 1-step procedures have been reported, including the synthesis of N-succinimidyl-4-([ 18 F]fluoromethyl)benzoate [22] and [ 18 F]fluoronicotinic acid 2,3,5,6-tetrafluorophenyl ([ 18 F]Fpy-TFP), a nicotinic acid derived active ester [23].…”