Pulse and CW EPR Oximetry Using Oxychip in Gemcitabine-Treated Murine Pancreatic Tumors

Mol Imaging Biol. 2023 Oct 2. doi: 10.1007/s11307-023-01859-w. Online ahead of print.

Abstract

Purpose: The goal of this work was to compare pO2 measured using both continuous wave (CW) and pulse electron paramagnetic resonance (EPR) spectroscopy. The Oxychip particle spin probe enabled longitudinal monitoring of pO2 in murine pancreatic tumor treated with gemcitabine during the course of therapy.

Procedures: Pancreatic PanO2 tumors were growing in the syngeneic mice, in the leg. Five doses of saline in control animals or gemcitabine were administered every 3 days, and pO2 was measured after each dose at several time points. Oxygen partial pressure was determined from the linewidth of the CW EPR signal (Bruker E540L) or from the T2 measured using the electron spin echo sequence (Jiva-25™).

Results: The oxygen sensitivity was determined from a calibration curve as 6.1 mG/mm Hg in CW EPR and 68.5 ms-1/mm Hg in pulse EPR. A slight increase in pO2 of up to 20 mm Hg was observed after the third dose of gemcitabine compared to the control. The maximum delta pO2 during the therapy correlated with better survival.

Conclusions: Both techniques offer fast and reliable oximetry in vivo, allowing to follow the effects of pharmaceutic intervention.

Keywords: EPR; Gemcitabine treatment; Hypoxia; Mouse pancreatic tumor model; Oximetry; Oxychip.