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Biocompatible Monophosphonated Trityl Spin Probe, HOPE71, for In Vivo Measurement of pO 2 , pH, and [P i ] by Electron Paramagnetic Resonance Spectroscopy.
- Source :
-
Analytical chemistry [Anal Chem] 2023 Jan 17; Vol. 95 (2), pp. 946-954. Date of Electronic Publication: 2022 Dec 20. - Publication Year :
- 2023
-
Abstract
- Hypoxia, acidosis, and elevated inorganic phosphate concentration are characteristics of the tumor microenvironment in solid tumors. There are a number of methods for measuring each parameter individually in vivo, but the only method to date for noninvasive measurement of all three variables simultaneously in vivo is electron paramagnetic spectroscopy paired with a monophosphonated trityl radical, pTAM/HOPE. While HOPE has been successfully used for in vivo studies upon intratissue injection, it cannot be delivered intravenously due to systemic toxicity and albumin binding, which causes significant signal loss. Therefore, we present HOPE71, a monophosphonated trityl radical derived from the very biocompatible trityl probe, Ox071. Here, we describe a straightforward synthesis of HOPE71 starting with Ox071 and report its EPR sensitivities to pO <subscript>2</subscript> , pH, and [P <subscript>i</subscript> ] with X-band and L-band EPR spectroscopy. We also confirm that HOPE71 lacks albumin binding, shows low cytotoxicity, and has systemic tolerance. Finally, we demonstrate its ability to profile the tumor microenvironment in vivo in a mouse model of breast cancer.
Details
- Language :
- English
- ISSN :
- 1520-6882
- Volume :
- 95
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Analytical chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 36537829
- Full Text :
- https://doi.org/10.1021/acs.analchem.2c03476