In vivo measurement of multiple tissue parameters using a single probe can provide a more complete and straighforward assemment of a particular disease state. For example, three physiological parameter of the tumor microenvironement that provide valuable insight to the tumor’s invasiveness, metastatic character, and therpeautic response include acidosis (pH), hypoxia (pO2), and interstitial inorganic phosphate concentration [Pi]. To our knowledge, the only method for non-invasive, concurrent measurement of these parameters is through Electron Paramagnetic Resonance (EPR) spectroscopy paired with a monophosphonated Finland trityl radical, HOPE, whose EPR spectrum is sensitive to pH, pO2, and [Pi]1. However, HOPE has some major limitations: lipophilic aggregation, albumin binding (which broadens the EPR signal), and intravenous toxicity. These shortcomings can be overcome through enhanced hydrophilicity. Here, we present the synthesis and characterization of a more hydrophilic and biocompatible monophosphonated trityl radical, HOPE71. The synthesis involves a two step sequence starting from the OX071 radical2. Then, we confirmed that the EPR spectrum for HOPE71 is sensitive to pH, pO2, and [Pi]. Additionally, we demonstrated that HOPE71 is more biocompatible with low cytotoxicity and no albumin binding. Lastly, we show a Matlab based application we developed for user-friendly fitting of the EPR spectra and extraction of pH, pO2, and [Pi].

HOPE71 – A biocompatible monophosphonated trityl spin probe for in vivo multiparametric electron paramagnetic resonance imaging and spectroscopy

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.