19F NMR imaging of a fluorinated anesthetic in a model system

Abstract

Previous fluorine-19 NMR imaging studies have focused primarily on potential applications of perhuorocarbon liquids (Z-3) and emulsions (4-6) as contrast agents for a variety of organs. One of the disadvantages in using perfluorinated agents for fluorine imaging is the multiplicity of resonances arising from chemically nonequivalent fluorine atoms. These widely spaced resonances (50150 ppm) introduce chemicalshift artifacts in the frequency-encoded spatial dimension and require a spectrum simplification (7) prior to image collection. The published in vivo i9F NMR studies of fluorinated anesthetics (8, 9), fluorinated glucose analogs (l&13), and fluorouracil(14, 15) have employed primarily spectroscopic analysis, rather than imaging techniques. The one-dimensional 19F mapping of the fluorinated anesthetic distribution in rat brain showed it to be nonuniform and time-dependent, but did not provide sufficient anatomical detail to assign the signals to known structures (16). Assessment of drug delivery and drug biodistribution provides a different, as yet unexplored, area for potential i9F imaging application. In this communication we demonstrate the parallel use of 19F with ‘H NMR imaging to determine the distribution of fluorinated drugs in biological tissues. As an example we chose the general anesthetic halothane (CF$HBrCl), which has a high lipid solubility, in the model host system provided by a green pepper. The distribution of halothane in a green pepper equilibrated with a saturated (15 n&f) aqueous solution of the anesthetic is illustrated in Fig. 1, which shows fluorine-19 (upper) and proton (lower) images of the same cross section. Halothane partitions preferentially into hydrophobic environments and thus is found in the oilcontaining seeds of the pepper. The proton image helps to define the structures within the pepper which contain this fluorinated compound. Both images are of the 5 mm thick slice obtained with a 6 in. imaging coil tuned to the fluorine-19 frequency. The images were produced using a modified spin-warp (17, 18) sequence with 7x = 300 ms and TE = 25 ms for the proton image, and 7R = 5 s and 7z = 25 ms for the fluorine19 image. The matrix size was 256 X 256 and the field of view 11 cm for both images. To increase the signal-to-noise ratio, four acquisitions for proton and eight acquisitions for fluorine19 images were averaged. The images were acquired on a General Electric 2T CSI spectrometer and processed using the 2D FT software. The concentration of