Journal Article Effect of Body Temperature on the Pharmacokinetics of a Triarylmethyl-Type Paramagnetic Contrast Agent Used in EPR Oximetry

Ken-ichiro, Matsumoto  ,  Hyodo, Fuminori  ,  B. Mitchell, James  ,  C. Krishna, Murali

79 ( 2 )  , pp.1212 - 1218 , 2018-01 , Wiley
Purpose: Pharmacokinetics of tri[8-carboxy-2,2,6,6-tetrakis(2-hydroxymethyl)benzo[1,2-d:4,5-d’]bis(1,3)dithio-4-yl]methyl radical (Oxo63) after a single bolus and/or continuous intravenous infusion was investigated in tumor bearing C3H mice with or without body temperature control while under anesthesia. Meshod: The in vivo time course of Oxo63 in blood was measured using X-band electron paramagnetic resonance (EPR) spectroscopy. Distribution of Oxo63 in normal muscle and tumor tissues was obtained using a surface coil resonator and a 700 MHz EPR spectrometer. The whole body distribution of Oxo63 was obtained by 300 MHz continuous wave (CW) EPR imaging. The high resolution 300 MHz time-domain EPR imaging was also carried out to probe the distribution of Oxo63.Results: Urination of mice was retarded at low body temperature making the concentration of Oxo63 in blood attain high levels. However, the concentration of Oxo63 in tumor tissue was lower with no control of body temperature than active body temperature control. The non-systemized blood flow in the tumor tissues may pool Oxo63 at lower body temperature. Conclusions: Pharmacokinetics of the contrast agent was found to be significantly affected by body temperature of the experimental animal and can influence the probe distribution and the image patterns.

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