IN-VIVO MONITORING OF FLUOROPYRIMIDINE METABOLITES - MAGNETIC-RESONANCE SPECTROSCOPY IN THE EVALUATION OF 5-FLUOROURACIL

Since 5-fluorouracil (5-FU) was synthesized in the late 1950s it has b ecome an important component of many anticancer treatment regimens. Th e increasing volume of literature accumulating about this drug is evid ence that the optimal administration schedule and its combination with modulators has yet to be determined. Much of the investigation of 5-F U, particularly in the clinical setting, has been in the development o f administration schedules based on plasma pharmacokinetic data. Parti cularly with the development of modulators of 5-FU, investigators are looking more closely at its intracellular tissue pharmacology and meta bolism. To study the tissue metabolism of 5-FU (and other drugs), pati ents often have to be willing to undergo invasive procedures, sometime s with significant discomfort, usually with little direct benefit to t heir management. The ability to conduct an investigation of the cellul ar effects of a drug in both tumor and normal tissue non-invasively wi ll not only be more acceptable to patients, resulting in better compli ance to protocols, but will give information about the in situ tissue which is not subject to the problems of invasive sampling techniques. Magnetic resonance spectroscopy is a non-invasive technique that has r ecently started to show potential in the area of investigating 5-FU me tabolism and its impact on tumor and patient outcome. Further developm ent of this method may ultimately have an impact on the investigation of any new anticancer agent.