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Invivo and exvivo magnetic resonance spectroscopy as applied to pharmacokinetic studies with anticancer agents: a review

Lookup NU author(s): Professor Herbie Newell, Dr Ross Maxwell, Emeritus Professor Bernard Golding


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The potential role of MRS in studying the pharmacokinetics of anticancer drugs is reviewed. In vivo 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 (C2-desamino-C2-methyl-N10-propargyl-2'-trifluoromethyl-5,8-dideazafolic acid). Studies in mice and rats have shown that hepatobiliary 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 vivo MRS is illustrated by studies on the urinary excretion of platinum complexes. H-1-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 Pt-195 NMR has been used to demonstrate in vivo reduction of this Pt(IV) complex to Pt(II) 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.

Publication metadata

Author(s): Newell DR, Maxwell RJ, Golding BT

Publication type: Article

Publication status: Published

Journal: NMR in Biomedicine

Year: 1992

Volume: 5

Issue: 5

Pages: 273-278

Print publication date: 01/09/1992

ISSN (print): 0952-3480

ISSN (electronic): 1099-1492