Skip to main content
Article thumbnail
Location of Repository

In vivo detection of ifosfamide by 31P-MRS in rat tumours: increased uptake and cytotoxicity induced by carbogen breathing in GH3 prolactinomas.

By L. M. Rodrigues, R. J. Maxwell, P. M. McSheehy, C. R. Pinkerton, S. P. Robinson, M. Stubbs and J. R. Griffiths


The direct detection and monitoring of anti-cancer drugs in vivo by magnetic resonance spectroscopy (MRS) may lead to improved anti-cancer strategies. 31P-MRS has been used to detect and quantify ifosfamide (IF) in vivo in GH3 prolactinomas and N-methyl-N-nitrosourea (MNU)-induced mammary tumours in rats. The average concentration of IF in the GH3 prolactinoma over the first 2 h following a dose of 250 mg kg-1 i.v. was calculated to be 0.42 micromol g-1 wet weight, with a half-life of elimination (t1/2) of 2-4 h. Carbogen (95% oxygen/5% carbon dioxide) breathing increased the amount of IF taken up by the GH3 prolactinoma by 50% (P<0.01) to 0.68 micromol g-1 wet weight, although t1/2 elimination rates were unchanged. IF was also detected in the liver in vivo, with a t1/2 of about 1 h. Carbogen breathing did not affect the maximum peak area (Cmax) or the t1/2 in the liver. Most importantly, the carbogen-induced increase in IF uptake by the tumour caused significant growth delay at all time points in the GH3 tumour growth between day 5 and day 12 (P< 0.01) compared with IF alone. These findings show that carbogen breathing has potential for increasing the efficacy of anti-cancer drugs. Isolated GH3 cells were sensitive to the parent drug (IF) in vitro (IC50 = 1.3 +/- 0.2 mM) suggesting that the GH3 cells may be either expressing P450 enzymes or are sensitive to the parent drug per se

Topics: Research Article
Publisher: Nature Publishing Group
OAI identifier:
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles


    1. (1988). Accurate quantification ofin vivo 31p NMR signals using the varible projection method and prior knowledge. Magn Reson Med6, 92-98 Vaupel P, Kallinowski F and OkunieffP
    2. (1967). Blood flow and oxygenation of tumours in mice. 1. Effects ofbreathing gases containing CO, at atmospheric pressure.
    3. (1996). Carbogeninduced oxygenation and blood flow changes within human tumours, monitored by Gradient Echo Magnetic Resonance Imaging.
    4. (1993). Determination of the urinary excretion of ifosfamide and its phosphorated metabolites by phosphorous-3 1 nuclear magnetic resonance spectroscopy.
    5. (1976). Studies on the human pharmacokinetics of isophosphamide (NSC 109724) Cancer Treat Rep 60: 451-458 Artemov

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.