Session: Advances in Spectroscopy:

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 [P_i]. 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 [P_i]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 [P_i]. 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].

Valery Khramtsov

Appearances