W. Wolf, C. Presant, V. Waluch
2003
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Abstract
Fluoropyrimidines occupy a unique niche in the noninvasive studies of drugs. For one, 5fluorouracil (5-FU), which was introduced by Heidelberger in the late 1950s as an anticancer agent, continues to be used widely for chemotherapy of colorectal and other cancers. And the physical properties of the fluorine atom make fluorinated drugs highly suitable for studies by two of the key imaging technologies. The 2-h 18F isotope allows fluorinated drugs to be studied using positron emission tomography (PET) methods, whereas the natural, 100% abundant 19F nuclide allows the use of nuclear magnetic resonance methods, including NMR spectroscopy (MRS) and imaging (MRI). Such noninvasive studies have been providing a unique insight into the fate of fluoropyrimidines at their target sites and are allowing us to gain a much better understanding of their mechanism of action. These noninvasive methods will allow, when properly used in clinical settings, objective assessments of whether the fluoropyrimidine chosen is likely to be effective in a given patient, as well as the development of a proper strategy for individualizing the dose and the dose regimen that is required to optimize chemotherapy for a given patient. Furthermore, these same methods can also provide an evidence-based evaluation of fluorinated pyrimidines in development, as well as assess the potential effect of any modulators. And finally, the noninvasive methods and techniques developed for the study of fluoropyrimidines are likely to document the potential of these methodologies for other noninvasive studies that can monitor and assist in the development of other drugs in oncology as well as in other areas of medicine.