SOX71, A Biocompatible Succinyl Derivative of the Triarylmethyl Radical OX071 for In Vivo Quantitative Oxygen Mapping Using Electron Paramagnetic Resonance.
EPR
Imaging
Oxygen
Spin probes
Triarylmethyl
Trityl
Journal
Molecular imaging and biology
ISSN: 1860-2002
Titre abrégé: Mol Imaging Biol
Pays: United States
ID NLM: 101125610
Informations de publication
Date de publication:
09 Nov 2023
09 Nov 2023
Historique:
received:
07
07
2023
accepted:
23
10
2023
revised:
27
09
2023
medline:
10
11
2023
pubmed:
10
11
2023
entrez:
9
11
2023
Statut:
aheadofprint
Résumé
This study aimed to develop a biocompatible oximetric electron paramagnetic resonance (EPR) spin probe with reduced self-relaxation, and sensitivity to oxygen for a higher signal-to-noise ratio and longer relaxation times at high oxygen concentration, compared to the reference spin probe OX071. SOX71 was synthesized by succinylation of the twelve alcohol groups of OX071 spin probe and characterized by EPR at X-Band (9.5 GHz) and at low field (720 MHz). The biocompatibility of SOX71 was tested in vitro and in vivo in mice. A pharmacokinetic study was performed to determine the best time frame for EPR imaging. Finally, a proof-of-concept EPR oxygen imaging was performed on a mouse model of a fibrosarcoma tumor. SOX71 was synthesized in one step from OX071. SOX71 exhibits a narrow line EPR spectrum with a peak-to-peak linewidth of 66 mG, similar to OX071. SOX71 does not bind to albumin nor show cell toxicity for the concentrations tested up to 5 mM. No toxicity was observed after systemic delivery via intraperitoneal injection in mice at twice the dose required for EPR imaging. After the injection, the probe is readily absorbed into the bloodstream, with a peak blood concentration half an hour, post-injection. Then, the probe is quickly cleared by the kidney with a half-life of ~ 45 min. SOX71 shows long relaxation times under anoxic condition (T SOX71, a succinylated derivative of OX071 was synthesized, characterized, and applied for in vivo EPR tumor oxygen imaging. SOX71 is highly biocompatible, and shows decreased sensitivity to oxygen and self-relaxation. This first report suggests that SOX71 is superior to OX071 for absolute oxygen mapping under a broad range of pO
Identifiants
pubmed: 37945971
doi: 10.1007/s11307-023-01869-8
pii: 10.1007/s11307-023-01869-8
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIGMS NIH HHS
ID : P20GM121322
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM133369
Pays : United States
Organisme : NIGMS NIH HHS
ID : GM143595
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20GM144230
Pays : United States
Organisme : NIGMS NIH HHS
ID : GM133369
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20GM103434
Pays : United States
Informations de copyright
© 2023. The Author(s), under exclusive licence to World Molecular Imaging Society.
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