Novel ¹H NMR approach to quantitative tissue oximetry using hexamethyldisiloxane

Abstract

19 F NMR spin-lattice relaxometry of hexafluorobenzene (HFB) has been shown to be a highly sensitive indicator of tumor oxygenation. In this study hexamethyldisiloxane (HMDSO) was identified as a proton NMR analog, and its potential as a probe for investigating dynamic changes in tissue oxygen tension (pO 2 ) was evaluated. HMDSO has a single proton resonance ‫؍␦(‬ -0.3 ppm) and the spin-lattice relaxation rate, R l ‫؍(‬ 1/T 1 ) exhibits a linear dependence on pO 2 : R 1 (s -1 ) ‫؍‬ 0.1126 ؉ 0.0013* pO 2 (torr) at 37°C. To demonstrate application in vivo, HMDSO was administered into healthy rat thigh muscle (100 l) and tumors (50 l). Local pO 2 was determined by using pulse-burst saturation recovery (PBSR) 1 H NMR spectroscopy to assess R 1 . Water and fat signals were effectively suppressed by frequency-selective excitation of the HMDSO resonance. Rat thigh muscle had a mean baseline pO 2 of 35 ؎ 11 torr, with a typical stability of ؎3 torr over 20 min, when the rats breathed air. Altering the inhaled gas to oxygen produced a significant increase in pO 2 to 100 -200 torr. In tumors, altering the inspired gas also produced significant (

Solid MRI contrast agents for long-term, quantitative in vivo oxygen sensing

“…5B) the previous set of experiments. Liquid siloxanes directly injected into a tissue site have a half-life of 35 h as reported in a recent paper by Kodibagkar et al (25). Neither the kinetics nor dynamic range of the sensors was reduced over the 4-wk period, suggesting at least one order of magnitude improvement over a simple liquid contrast agent injection.…”

“…Molecular oxygen is paramagnetic and reduces the longitudinal relaxation time of the hydrogen nuclei on neighboring molecules (Supporting Information, section S1). The longitudinal relaxation time of linear siloxanes has previously been reported to vary with oxygen partial pressure (25), and we exploit this property and use the materials to measure oxygen tension. The MR signals obtained from siloxanes are dependent on oxygen partial pressure and are used directly for the measurements, unlike metal-ion based contrast agents that modulate the relaxivity of surrounding water protons.…”

“…A variety of contrast agents have been used in MRI studies to highlight tissue structures; "smart" contrast agents, designed to respond to changing environmental conditions, are gaining importance in both the research and clinical community (29). Targets of these contrast agents include specific metabolites such as oxygen (25) and pH (30) and proteins involved in enzymatic reactions (31). Similarly, a number of biocompatible polymers, in addition to the silicones used in this study, could be used to hold these contrast agents in place.…”

“…Using this principle, we have designed a contrast agent sensitive to oxygen, which is composed of dodecamethylpentasiloxane as the responsive material and polydimethylsiloxane as the matrix material. A rodent inspired-gas model demonstrated that these materials are functionally stable in vivo for at least 1 mo, which represents an order of magnitude improvement over an injection of liquid siloxane [Kodibagkar VD, et al (2006) …”

Theranostic Probes for Targeting Tumor Microenvironment: An Overview

“…This series shows evolution of 18 Magnetic Resonance Spectroscopy (MRS) has evolved with probes for determination of the level of deoxygenation using the relaxation of Hexamethyldisoloxane (HMDSO) such as 1H MRS [24]. It measures the tension of oxygen in prostate cancer cells after intravenous injection [25]. Furthermore, perfluorocarbons (19F MRS) are used in combination with nitroimidazole to design a probe, namely 2-nitro-α-[(2, 2, 2-trifluoroethoxy) methyl]-imidazole-1-ethanol, that undergoes reduction when it binds to the endogenous molecules of hypoxic cells.…”