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A new class of fluorinated A2A adenosine receptor agonist with application to last-step enzymatic [18F]fluorination for PET imaging

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posted on 15.01.2019, 09:22 by Phillip T. Lowe, Sergio Dall'Angelo, Thea Mulder-Krieger, Adriaan P. IJzerman, Matteo Zanda, David O'Hagan
The A2A adenosine receptor belongs to a family of G-coupled protein receptors that have been subjected to extensive investigation over the last few decades. Due to their prominent role in the biological functions of the heart, lungs, CNS and brain, they have become a target for the treatment of illnesses ranging from cancer immunotherapy to Parkinson's disease. The imaging of such receptors by using positron emission tomography (PET) has also been of interest, potentially providing a valuable tool for analysing and diagnosing various myocardial and neurodegenerative disorders, as well as offering support to drug discovery trials. Reported herein are the design, synthesis and evaluation of two new 5′-fluorodeoxy-adenosine (FDA)-based receptor agonists (FDA-PP1 and FDA-PP2), each substituted at the C-2 position with a terminally functionalised ethynyl unit. The structures enable a synthesis of 18F-labelled analogues by direct, last-step radiosynthesis from chlorinated precursors using the fluorinase enzyme (5′-fluoro-5′-deoxyadenosine synthase), which catalyses a transhalogenation reaction. This delivers a new class of A2A adenosine receptor agonist that can be directly radiolabelled for exploration in PET studies.

Funding

Engineering and Physical Sciences Research Council. Grant Number: EP/M01262X/1.

History

School

  • Science

Department

  • Chemistry

Published in

ChemBioChem

Volume

18

Issue

21

Pages

2156 - 2164

Citation

LOWE, P.T. ... et al, 2017. A new class of fluorinated A2A adenosine receptor agonist with application to last-step enzymatic [18F]fluorination for PET imaging. ChemBioChem, 18 (21), pp.2156-2164.

Publisher

© Wiley

Version

AM (Accepted Manuscript)

Publisher statement

This work is made available according to the conditions of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) licence. Full details of this licence are available at: https://creativecommons.org/licenses/by-nc-nd/4.0/

Publication date

2017-08-29

Notes

This is the peer reviewed version of the following article: LOWE, P.T. ... et al, 2017. A new class of fluorinated A2A adenosine receptor agonist with application to last-step enzymatic [18F]fluorination for PET imaging. ChemBioChem, 18 (21), pp.2156-2164, which has been published in final form at https://doi.org/10.1002/cbic.201700382. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.

ISSN

1439-4227

eISSN

1439-7633

Language

en