In vivo and ex vivo magnetic resonance spectroscopy as applied to pharmacokinetic studies with anticancer agents: a review

✍ Scribed by David R. Newell; Ross J. Maxwell; Bernard T. Golding

• Publisher: John Wiley and Sons
• Year: 1992
• Tongue: English
• Weight: 782 KB
• Volume: 5
• Category: Article
• ISSN: 0952-3480
• DOI: 10.1002/nbm.1940050514

✦ Synopsis

The potential role of MRS in studying the pharmacokinetics of anticancer drugs is reviewed. I n vim and ex vivo MRS has been used extensively in studies with fluoropyrimidines. Results from preclinical models have demonstrated that biochemical modulation of 5-fluorouracil metabolism can be demonstrated by MRS. The more general potential of MRS is illustrated by studies with the antifolate CB3988 (C-desamino-Cz-methy1~"propargyl-2'-trifluoromethyl-5,8-dideazafolic acid). Studies in mice and rats have shown that hepatobdiary clearance and renal elimination can be measured non-invasively by MRS. Comparison of half-lives derived from MRS and high performance liquid chromatography data gave reasonable agreement. In addition, MRI was used to localize drug-derived material within the abdominal cavity. The application of ex vim MRS is illustrated by studies on the urinary excretion of platinum complexes. 'H-MRS has been used to demonstrate the presence of the cyclobutanedicarboxylate leaving group, both free and platinum bound, in the urine of patients treated with carboplatin. With iproplatin 19'Pt NMR has been used to demonstrate in vim reduction of this Pt(IV) complex to Pt(I1) complexes. Finally, the application of MRS to the study of the molecular pharmacology of alkylating agents (a nitrogen mustard and N-methyl-N-nitrosourea) is discussed.