title: Pharmacokinetics of a triarylmethyl-type paramagnetic spin probe used in EPR oximetry.
abstract: The paramagnetic spin probe Oxo63 is used in oximetric imaging studies based on electron paramagnetic resonance (EPR) methods by monitoring the oxygen-dependent linewidth while minimizing the contributions from self-broadening seen at high probe concentrations. Therefore, it is necessary to determine a suitable dose of Oxo63 for EPR-based oxygen mapping where the self-broadening effects are minimized while signal intensity adequate for imaging can be realized. A constant tissue concentration of spin probe would be useful to image a subject and assess changes in pO2 over time; accumulation or elimination of the compound in specific anatomical regions could translate to and be mistaken for changes in local pO2, especially in OMRI-based oximetry. The in vivo pharmacokinetics of the spin probe, Oxo63, after bolus and/or continuous intravenous infusion was investigated in mice using a novel approach with X-band EPR spectroscopy. The results show that the half-life in blood was 17-21 min and the clearance by excretion was 0.033-0.040 min(-1). Continuous infusion following a bolus injection of the probe was found to be effective to obtain stable plasma concentration as well as image intensity to permit reliable pO2 estimates.
authors.affiliation: Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892-1002, USA.
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Sean
authors.initials: S
authors.lastname: English
authors.forename: John
authors.initials: J
authors.lastname: Yoo
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Yamada
authors.forename: Nallathamby
authors.initials: N
authors.lastname: Devasahayam
authors.forename: John A
authors.initials: JA
authors.lastname: Cook
authors.forename: James B
authors.initials: JB
authors.lastname: Mitchell
authors.forename: Sankaran
authors.initials: S
authors.lastname: Subramanian
authors.forename: Murali C
authors.initials: MC
authors.lastname: Krishna
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000493:pharmacokinetics*; D017352:Echo-Planar Imaging / Q000379:methods*; D005260:Female; D006575:Heterocyclic Compounds, 3-Ring / Q000493:pharmacokinetics; D049673:History, 20th Century; D051379:Mice; D008809:Mice, Inbred C3H; D010092:Oximetry / Q000379:methods*; D013113:Spin Labels
chemical_list: D003287:Contrast Media; D006575:Heterocyclic Compounds, 3-Ring; C495909:Oxo63; D013113:Spin Labels