Issues of normal tissue toxicity in patient and animal studies–effect of carbogen breathing in rats after 5-fluorouracil treatment.

Abstract:: Non-invasive magnetic resonance spectroscopy (MRS) can be used in the clinic to monitor the pharmacokinetics of the chemotherapeutic drug 5-fluorouracil (5-FU) and the effects of modifiers. We report two studies of 5-FU toxicity in normal tissue--one with patients and the other an animal study. 1) 19F MRS signals from fluoronucleotides, cytotoxic anabolites of 5-FU metabolism, were observed in the livers of two patients treated with 5-FU for colorectal cancer, shown by computed tomography (CT) and ultrasound (US) to have 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 is under trial in patients. This study demonstrates that there were no significant effects of carbogen breathing on the levels of 5-FU and its metabolites in normal rat tissues, or on the histology of the tissues assessed after treatment.

Authors:: JR Griffiths, DJ McIntyre, FA Howe, PM McSheehy, Ojugo ASE, LM Rodrigues, P Wadsworth, NM Price, F Lofts, G Nicholson, K Smid, P Noordhuis, GJ Peters, M Stubbs

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