Issues of normal tissue toxicity in patient and animal studies - Effect ofcarbogen breathing in rats after 5-fluorouracil treatment

Non-invasive magnetic resonance spectroscopy (MRS) can be used in the clini c to monitor the pharmacokinetics of the chemotherapeutic drug 5-fluorourac il (5-FU) and the effects of modifiers. We report two studies of 5-FU toxic ity in normal tissue-one with patients and the other an animal study. 1) F- 19 MRS signals from fluoronucleotides, cytotoxic anabolites of 5-FU metabol ism, were observed in the livers of two patients treated with 5-FU for colo rectal cancer, shown by computed tomography (CT) and ultrasound (US) to hav e no liver metastases. This is the first report of non-invasive monitoring of toxic 5-FU metabolites in normal human tissues. 2) In animals, carbogen breathing enhances tumour uptake and the efficacy of 5-FU, and the method i s under trial in patients. This study demonstrates that there were no signi ficant effects of carbogen breathing on the levels of 5-FU and its metaboli tes in normal rat tissues, or on the histology of the tissues assessed afte r treatment.