Fluorine‐18 labelling of a series of potential EGFRvIII targeting peptides with a parallel labelling approach using [¹⁸F]FPyME

Abstract

There is growing interest in the use of radiolabelled peptides as receptor targeting agents for diagnostic imaging of various cancer types using positron emission tomography. In this work, 1-18 F]FPyME) has been used for parallel fluorine-18 labelling of PEPHC1, a peptide selective towards the cancer-specific mutation of the epidermal growth factor receptor (EGFRvIII), and a number of truncated and mutated analogues. Conjugation of the peptides with [18 F]FPyME was achieved within 10 min in non-decay-corrected radiochemical yields of 30-50%. The high yield of the conjugation reaction combined with its short synthesis time allows the labelling of several peptides from a single batch of [18 F]FPyME.

18F‐Labeling of Sensitive Biomolecules for Positron Emission Tomography

“…Figure 12B depicts a recent collection of 18 F-labeled maleimides from a variety of reliable labeling methodologies that demonstrated the diversity of these thiol-selective prosthetic groups. Maleimide based prosthetic groups such as 4-((4- [18 F]fluorobenzylidene) aminooxybutyl) maleimide ( [18 F]FBAM, 71 ), [66] 1-[3-(2- [18 F]fluoropyridin-3-yloxy)propyl]pyrrole-2,5-dione ( [18 F]FPyME, 72 ), [67] N -[2-(4- [18 F]fluorobenzamido)ethyl]maleimide ( [18 F]FBEM, 73 ), [68] [18 F]FDG-maleimidehexyloxime ( [18 F]FDG-MHO, 74 ), 40a N -5- [18 F]fluoropentylmaleimide ( [18 F]FPenM, 75 ), [69] N -(2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)ethyl)-6- [18 F]fluoronicotinamide ( [18 F]FNEM, 76 ), [70] [18 F]SiFApMaleimide ( 77 ), [71] 4-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)benzenesulfonyl fluoride ( 78 ) [54] and [18 F]fluorobutyl ethacrynic amide ( [18 F]FBuEA, 79 ) [72] have been used to couple with biomolecules via thiol-selective Michael additions (Figure 12B). …”

Novel 2,4,5‐Trisubstituted Pyridines as Key Intermediates for the Preparation of the TSPO Ligand 6‐F‐PBR28: Synthesis and Full 1H and 13C NMR Characterization

“…Besides being rapid (a few minutes) and often reported to proceed with high yields (>70%), these reactions lead to a positioning of the radioactive atom in the probe that is relatively stable metabolically (C(sp 2 )―F bond), a considerable advantage when compared with the traditionally dominating aliphatic nucleophilic radiofluorination methodology (C(sp 3 )―F bond formation) . For these reasons, we have a long‐standing interest in molecules bearing a 2‐fluoropyridine moiety, and we have already reported several 2‐[ 18 F]fluoropyridinyl‐containing structures, for use either as radioligands or as reagents dedicated to the radiolabeling of more complex structures such as oligonucleotides, peptides, or proteins by prosthetic conjugation approaches.…”

[18F]Fluoride labelling of macromolecules in aqueous conditions: silicon and boroaryl‐based [18F]fluorine acceptors, [18F]FDG conjugation and Al18F chelation

“…Conjugation of the synthon N ‐succinimidyl‐4‐ 18 F‐fluorobenzoate to primary NH 2 groups on peptides and proteins serves as a useful method for [ 18 F]labelling; however, this synthon can also conjugate with secondary NH 2 groups on lysine residues within the peptide, potentially altering the character of the molecule. Thiol‐containing peptides can be reacted with maleimide‐containing prosthetic groups, for example, N ‐(2‐(4‐[ 18 F]fluorobenzamido)ethyl)maleimide or 1‐[3‐(2‐[ 18 F]fluoropyridin‐3‐yloxylpropylpyrrole‐2,5dione[ 18 F] (Figure ). The latter can be produced with specific activities of 74–125 GBq/µmol.…”

“…Maleimide‐containing prosthetic groups for conjugation with thiol‐containing peptides (reproduced from Denholt et al …”