Synthesis, bioconjugation and stability studies of [18F]ethenesulfonyl fluoride

Fluorine‐18 labelled prosthetic groups (PGs) are often necessary for radiolabelling sensitive biological molecules such as peptides and proteins. Several shortcomings, however, often diminish the final yield of radiotracer. In an attempt to provide higher yielding and operationally efficient tools f...

Full description

Saved in:
Bibliographic Details
Published in:Journal of labelled compounds & radiopharmaceuticals 2018-09, Vol.61 (11), p.847-856
Main Authors: Zhang, Bo, Pascali, Giancarlo, Wyatt, Naomi, Matesic, Lidia, Klenner, Mitchell A., Sia, Tiffany R., Guastella, Adam J., Massi, Massimiliano, Robinson, Andrea J., Fraser, Benjamin H.
Format: Article
Language:English
Subjects:
Amino acids
Animals
Cattle
Chemical synthesis
Chemistry Techniques, Synthetic
Conjugates
Conjugation
Drug Stability
Fluorides
Fluorides - chemical synthesis
Fluorides - chemistry
Fluorides - metabolism
Fluorine
Fluorine isotopes
Fluorine Radioisotopes - chemistry
Fluorine Radioisotopes - metabolism
fluorine‐18
Insulin - metabolism
Isotope Labeling
Lasers, Excimer
Michael acceptor
Microfluidics
peptide labelling
Peptides
Positron emission
Prostheses
prosthetic group
Prosthetic groups
Proteins
Radioactive tracers
Radiochemistry
Radiolabelling
Serum Albumin, Bovine - metabolism
Stability analysis
Substrates
Sulfones - chemical synthesis
Sulfones - chemistry
Sulfones - metabolism
sulfonyl fluoride
Tomography
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Fluorine‐18 labelled prosthetic groups (PGs) are often necessary for radiolabelling sensitive biological molecules such as peptides and proteins. Several shortcomings, however, often diminish the final yield of radiotracer. In an attempt to provide higher yielding and operationally efficient tools for radiolabelling biological molecules, we describe herein the first radiochemical synthesis of [18F]ethenesulfonyl fluoride ([18F]ESF) and its Michael conjugation with amino acids and proteins. The synthesis of [18F]ESF was optimised using a microfluidic reactor under both carrier‐added (c.a.) and no‐carrier‐added (n.c.a.) conditions, affording, in a straightforward procedure, 30‐50% radiochemical yield (RCY) for c.a. [18F]ESF and 60‐70% RCY for n.c.a. [18F]ESF. The conjugation reactions were performed at room temperature using 10 mg/mL precursor in aqueous/organic solvent mixtures for 15 min. The radiochemical stability of the final conjugates was evaluated in injectable formulation and rat serum, and resulted strongly substrate dependent and generally poor in rat serum. Therefore, in this work we have optimised a straightforward synthesis of [18F]ESF and its Michael conjugation with model compounds, without requiring chromatographic purification. However, given the general low stability of the final products, further studies will be required for improving conjugate stability, before assessing the use of this PG for PET imaging. We report herein the radiosynthesis of [18F]ethenesulfonyl fluoride ([18F]ESF), that proceeds straightforwardly without the need of chromatographic purification. We then investigated the use of [18F]ESF as a new prosthetic group on amino acids, insulin and BSA. While the conjugation methodology and the purification processes were simple and efficient, the stabilities of the final products are strongly substrate‐dependent, and generally low in serum.
ISSN:0362-4803
1099-1344
DOI:10.1002/jlcr.3667