F-19
In Vivo Spectroscopy
Fluorinated compounds are widely used in medicine in the form of anesthetics, perfluorocarbon blood substitutes (synthetic oxygen carriers), radiopaque contrast agents, and drugs (5-FU, 5-Fluorouracil) with fluorinated functionality or substituents (Ref. 1). In Nuclear Magnetic Resonance (NMR) fluorine-19 has been used extensively as a chemical probe (Ref. 2). Its favorable NMR properties make it an ideal element to be used for in vivo studies:

Stable isotope
100% Natural abundance
Spin 1/2
Gyromagnetic ratio of 40MHz/T (94% of H-1)
Sensitivity 83% of H-1 at constant field
Chemical shift range over 200 ppm

The gyromagnetic ratio of F-19 is only 6% lower than H-1 making it "accessible" by readjustment of standard (H-1) MRI RF components. The NMR F-19 sensitivity is comparable with that of H-1. However, unlike the other light elements (H,O,C,N, etc.) there is virtually no natural fluorine present in animal tissue. This fact improves the reliablity of analytical techniques, localization methods, and, combined with the large (over 200 ppm) chemical shift range of F-19, facilitates accurate spectroscopic identification and characterization of exogenous compounds in vivo (Ref. 3). In addition, unlike PET scans using F-18, specific chemical structure information is available in vivo with F-19.

F-19 imaging, both spectrally resolved and unresolved, appears to be of great interest to the medical community. A complete lack of natural background and high tolerance of the body to certain fluorinated compounds (anesthetics and blood substitution agents) make F-19 imaging an attractive possibilty (Ref. 4,5,6).

Currently, in vivo F-19 spectroscopic expertise may be divided into four areas:

Anesthesiology - spectroscopy and bio-distributionof fluorinated agents such as halothane, methoxyfluorane, and isofluorane in animal brain, muscle, and tumors (Ref. 7,8,9,10,11,12,13,14). These studies demonstrate previously unobtainable data on the distribution and chemistry of commonly used anesthetic agents. it can be anticipated that human use will produce significant benefits in optimizing dose, in minimizing side effects, and in investigating brain function.

Vascular function - studies of cardiac function, blood flow, oxygen perfusion, and oxygen transfer in blood substitutes (Ref. 15,16,17,18,19,20,21). Assessment of organ perfusion (cerebral and kidney perfusion) using direct methods is possible leading to potential elimination of less effective radiographic or nuclear medicine techniques which carry a greater risk. Direct measurement of oxygen concentrations and oxygen effects can be observed.

Brain metabolism - studies of local cerebral glucose utlization rates by PET with the radiolabeled glucose analog 2-fluoro-2-deoxy-D-glucose (2FDG) suffer from a lack of chemical specificity. F-19 NMR resolves this problem by producing direct evidence of phosphorylation at high rates and can show persistance in the brain with time constants much longer than the half-life of the F-18 radionucleus used by PET studies (Ref 22,23,24,25,26,27).

Drug metabolism - previously used in following the competing catabolic pathway of chemotherapuetic agents in animals and humans. The very common chemotherapy drug, 5-fluorouracil, and its derviatives has been extensively studied with F-19 NMR (Ref. 28,29,30,31,32,33,34,35,36,37). Delivery of the drug to tumors sites as well as catabolism in the liver has been studied in humans and appears to have significantpotential in enhancement of the course of therapy.

5-FU, 5-Fluorouracil

F-19 spectra of a well known fluorinated chemotherapeutic drug, 5-fluorouracil, and its metabolites can be obtainable in the liver and in tumors of patients undergoing cancer chemotherapy (Ref. 34,35,36,37).

In Vivo F-19 stack plot!

F-19 Stack Plot

In Vivo F-19 contour plot!

F-19 Countor Plot

F-19 REFERENCES

Last real update for this page: 13-Mar-98

(WIP - works in progress)