Detecting hypoxia: In vitro using 18F-pretargeted IEDDA "click" chemistry in live cells

Louis Allott; Cen Chen; Marta Braga; Sau Fung Jacob Leung; Ning Wang; Chris Barnes; Diana Brickute; Laurence Carroll; Eric O. Aboagye

doi:10.1039/d1ra02482e

Detecting hypoxia: In vitro using ¹⁸F-pretargeted IEDDA "click" chemistry in live cells

Louis Allott, Cen Chen, Marta Braga, Sau Fung Jacob Leung, Ning Wang, Chris Barnes, Diana Brickute, Laurence Carroll, Eric O. Aboagye

School of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

We have exemplified a pretargeted approach to interrogate hypoxia in live cells using radioactive bioorthogonal inverse electron demand Diels-Alder (IEDDA) "click"chemistry. Our novel 18F-tetrazine probe ([18F]FB-Tz) and 2-nitroimidazole-based TCO targeting molecule (8) showed statistically significant (P < 0.0001) uptake in hypoxic cells (ca. 90 %ID per mg) vs. normoxic cells (<10 %ID per mg) in a 60 min incubation of [18F]FB-Tz. This is the first time that an intracellularly targeted small-molecule for IEDDA "click"has been used in conjunction with a radioactive reporter molecule in live cells and may be a useful tool with far-reaching applicability for a variety of applications.

Original language	English (US)
Pages (from-to)	20335-20341
Number of pages	7
Journal	RSC Advances
Volume	11
Issue number	33
DOIs	https://doi.org/10.1039/d1ra02482e
State	Published - Jun 7 2021

ASJC Scopus subject areas

General Chemical Engineering
General Chemistry

Access to Document

10.1039/d1ra02482e

Cite this

@article{2e17491890c245d98b6f76d09ebdb5df,

title = "Detecting hypoxia: In vitro using 18F-pretargeted IEDDA {"}click{"} chemistry in live cells",

abstract = "We have exemplified a pretargeted approach to interrogate hypoxia in live cells using radioactive bioorthogonal inverse electron demand Diels-Alder (IEDDA) {"}click{"}chemistry. Our novel 18F-tetrazine probe ([18F]FB-Tz) and 2-nitroimidazole-based TCO targeting molecule (8) showed statistically significant (P < 0.0001) uptake in hypoxic cells (ca. 90 %ID per mg) vs. normoxic cells (<10 %ID per mg) in a 60 min incubation of [18F]FB-Tz. This is the first time that an intracellularly targeted small-molecule for IEDDA {"}click{"}has been used in conjunction with a radioactive reporter molecule in live cells and may be a useful tool with far-reaching applicability for a variety of applications.",

author = "Louis Allott and Cen Chen and Marta Braga and Leung, {Sau Fung Jacob} and Ning Wang and Chris Barnes and Diana Brickute and Laurence Carroll and Aboagye, {Eric O.}",

note = "Funding Information: This work was supported by the Imperial College NIHR Biomedical Research Centre award (WSCC_P62585) and the Medical Research Council grant (MC-A652-5PY80). C. C. was funded by King's and Imperial College London EPSRC Centre for Doctoral Training in Medical Imaging (EP/L015226/1). Publisher Copyright: {\textcopyright} The Royal Society of Chemistry.",

year = "2021",

month = jun,

day = "7",

doi = "10.1039/d1ra02482e",

language = "English (US)",

volume = "11",

pages = "20335--20341",

journal = "RSC Advances",

issn = "2046-2069",

publisher = "Royal Society of Chemistry",

number = "33",

}

TY - JOUR

T1 - Detecting hypoxia

T2 - In vitro using 18F-pretargeted IEDDA "click" chemistry in live cells

AU - Allott, Louis

AU - Chen, Cen

AU - Braga, Marta

AU - Leung, Sau Fung Jacob

AU - Wang, Ning

AU - Barnes, Chris

AU - Brickute, Diana

AU - Carroll, Laurence

AU - Aboagye, Eric O.

N1 - Funding Information: This work was supported by the Imperial College NIHR Biomedical Research Centre award (WSCC_P62585) and the Medical Research Council grant (MC-A652-5PY80). C. C. was funded by King's and Imperial College London EPSRC Centre for Doctoral Training in Medical Imaging (EP/L015226/1). Publisher Copyright: © The Royal Society of Chemistry.

PY - 2021/6/7

Y1 - 2021/6/7

N2 - We have exemplified a pretargeted approach to interrogate hypoxia in live cells using radioactive bioorthogonal inverse electron demand Diels-Alder (IEDDA) "click"chemistry. Our novel 18F-tetrazine probe ([18F]FB-Tz) and 2-nitroimidazole-based TCO targeting molecule (8) showed statistically significant (P < 0.0001) uptake in hypoxic cells (ca. 90 %ID per mg) vs. normoxic cells (<10 %ID per mg) in a 60 min incubation of [18F]FB-Tz. This is the first time that an intracellularly targeted small-molecule for IEDDA "click"has been used in conjunction with a radioactive reporter molecule in live cells and may be a useful tool with far-reaching applicability for a variety of applications.

AB - We have exemplified a pretargeted approach to interrogate hypoxia in live cells using radioactive bioorthogonal inverse electron demand Diels-Alder (IEDDA) "click"chemistry. Our novel 18F-tetrazine probe ([18F]FB-Tz) and 2-nitroimidazole-based TCO targeting molecule (8) showed statistically significant (P < 0.0001) uptake in hypoxic cells (ca. 90 %ID per mg) vs. normoxic cells (<10 %ID per mg) in a 60 min incubation of [18F]FB-Tz. This is the first time that an intracellularly targeted small-molecule for IEDDA "click"has been used in conjunction with a radioactive reporter molecule in live cells and may be a useful tool with far-reaching applicability for a variety of applications.

UR - http://www.scopus.com/inward/record.url?scp=85108535031&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85108535031&partnerID=8YFLogxK

U2 - 10.1039/d1ra02482e

DO - 10.1039/d1ra02482e

M3 - Article

C2 - 34178309

AN - SCOPUS:85108535031

SN - 2046-2069

VL - 11

SP - 20335

EP - 20341

JO - RSC Advances

JF - RSC Advances

IS - 33

ER -

Detecting hypoxia: In vitro using ¹⁸F-pretargeted IEDDA "click" chemistry in live cells

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this