New techniques in the pharmacokinetic analysis of cancer drugs. III. Nuclear magnetic resonance.
Nuclear magnetic resonance spectroscopy and imaging are non-invasive methods for monitoring the metabolism and distribution of anti-cancer drugs in tumours or other tissues. 19F NMR provides the easiest approach but requires a "built-in" fluorine atom in the drug of interest (eg 5-fluorouracil) or the incorporation of fluorine with minimal perturbance of a drug's properties. 2H NMR has also been used but has an effective sensitivity about 10- to 100-fold less than 19F. 1H and 13C are likely to be useful as non-perturbing NMR probes for future pharmacokinetic studies. The method is intrinsically insensitive, with a detection limit in the range of 0.01 to 0.1 mmol for fluorinated drugs. Techniques for absolute quantitation and for reliable localization to specific tissues and tumours are now available but have only rarely been applied in pharmacokinetic studies in the current literature. The incorporation of in vivo NMR measurements in a drug development programme should help to explain the differences found between drug activity in vitro, in solid animal tumour models and in cancer patients. It may also be possible to optimize drug selection or mode of administration for an individual patient.
Maxwell
R J
RJ
CRC Biomedical Magnetic Resonance Research Group, St George's Hospital Medical School, London.
D000970:Antineoplastic Agents / Q000032:analysis* / Q000493:pharmacokinetics; D005472:Fluorouracil / Q000032:analysis; D005492:Folic Acid / Q000031:analogs & derivatives / Q000032:analysis; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008920:Misonidazole / Q000032:analysis; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism
D000970:Antineoplastic Agents; C066506:CB 3988; D008920:Misonidazole; D005492:Folic Acid; D005472:Fluorouracil