A Compact and Synthetically Accessible Fluorine-18 Labelled Cyclooctyne Prosthetic Group for Labelling of Biomolecules by Copper-Free Click Chemistry

Emily Murrell; Michael S Kovacs; Leonard G Luyt

doi:10.1002/cmdc.201800334

A Compact and Synthetically Accessible Fluorine-18 Labelled Cyclooctyne Prosthetic Group for Labelling of Biomolecules by Copper-Free Click Chemistry

ChemMedChem. 2018 Aug 20;13(16):1625-1628. doi: 10.1002/cmdc.201800334. Epub 2018 Jul 23.

Authors

Emily Murrell¹, Michael S Kovacs^{2

3}, Leonard G Luyt^{1

4

5}

Affiliations

¹ Department of Chemistry, University of Western Ontario, 1151 Richmond Street, London, ON, N6A 5B7, Canada.
² Lawson Health Research Institute, 268 Grosvenor Street, London, ON, N6A 4V2, Canada.
³ Departments of Medical Imaging and Medical Biophysics, University of Western Ontario, 1151 Richmond Street, London, ON, N6A 5B7, Canada.
⁴ Department of Oncology, University of Western Ontario, 1151 Richmond Street, London, ON, N6A 5B7, Canada.
⁵ London Regional Cancer Program, Lawson Health Research Institute, 790 Commissioners Road East, London, ON, N6A 4L6, Canada.

PMID: 29923326
DOI: 10.1002/cmdc.201800334

Abstract

A new fluorine-containing azadibenzocyclooctyne (ADIBO-F) was designed using a synthetically accessible pathway. The fluorine-18 prosthetic group was prepared from its toluenesulfonate precursor and isolated in 21-35 % radiochemical yield in 30 minutes of synthetic time. ADIBO-F has been incorporated into azide-functionalized, cancer-targeting peptides through a strain-promoted alkyne-azide cycloaddition with high radiochemical yields and purities. The final products are novel peptide-based positron emission tomography (PET) imaging agents that possess high affinities for their targets, growth hormone secretagogue receptor 1a (GHSR-1a) and gastrin-releasing peptide receptor (GRPR), with IC₅₀ values of 9.7 and 0.50 nm, respectively. This is a new and rapid labelling option for the incorporation of fluorine-18 into biomolecules for PET imaging.

Keywords: click chemistry; fluorine; imaging agents; peptides; radiopharmaceuticals.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alkynes / chemical synthesis
Alkynes / chemistry
Bombesin / analogs & derivatives*
Bombesin / chemical synthesis
Click Chemistry
Cycloaddition Reaction
Cyclooctanes / chemical synthesis
Cyclooctanes / chemistry*
Fluorine Radioisotopes
Ghrelin / analogs & derivatives*
Ghrelin / chemical synthesis
Heterocyclic Compounds, 3-Ring / chemical synthesis
Heterocyclic Compounds, 3-Ring / chemistry*
Isotope Labeling / methods
Molecular Structure
Positron-Emission Tomography / methods
Proof of Concept Study
Radiopharmaceuticals / chemical synthesis
Radiopharmaceuticals / chemistry*

Substances

Alkynes
Cyclooctanes
Fluorine Radioisotopes
Ghrelin
Heterocyclic Compounds, 3-Ring
Radiopharmaceuticals
Fluorine-18
Bombesin