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In vivo measurement of the hypoxia marker EF5 using ¹⁹F magnetic resonance spectroscopy Hoff, Michael Nicholas

Abstract

¹⁹FMagnetic Resonance Spectroscopy (MRS) of the 2-nitroimidazole EF5 [2-(2-nitro-1Himidazol-1-y1)-N-(2,2,3,3,3-pentafluoropropyl) acetamide] injected intravenously (IV) into DDS mice with implanted Shionogi prostate tumours produced a negative correlation in two of three sample groups when MRS signal was compared with hypoxic fraction determined by flow cytometry. The negative correlations in mouse groups a and b generated P values via regression analysis of 0.006 and 0.073 respectively. The viability of cells in group a was 34 °± 26 %, whereas group b and c had a combined viability of 7.2 ± 5.8%. No signal resulted from scans of disaggregated or enzymatically digested tumour cells. Measurements of MRS signal over time yielded a steady decline of detectable signal to at least 7 hours after intraperitoneal (IP) injection of EF5 in all mice; one mouse produced signal up to 72 hours after injection. Results were obtained using a 2 cm diameter, 1.4cm length solenoid volume coil with distributed capacitance for maximal SNR. Signal was acquired on a 7.05 T Bruker scanner 2-3 hours following IV or IP injection of EF5. Avertin was used for anaesthesia predominately, since the inhaled anaesthetics isofluorane and halothane contained fluorine signal. Sample absolute quantification tests were made to determine the accuracy of measurements, with resulting coefficients of variance equal to 2.4% and 4.2% for XWIN-NMR and AMARES quantification algorithms respectively. Results confirmed that MRS of EF5 in mice is an unsuitable technique for the determination of EF5 bound to cellular macromolecules. The desire to quantify EF5 bound to macromolecules non-invasively in hypoxic regions would serve as a valuable prognostic tool for cancer therapy. The defined method can instead provide an indicator of the lack of macromolecular binding and potentially the degree of thiol binding in certain controlled tumour environments.

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