Abstract |
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.
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Authors | L M Rodrigues, R J Maxwell, P M McSheehy, C R Pinkerton, S P Robinson, M Stubbs, J R Griffiths |
Journal | British journal of cancer
(Br J Cancer)
Vol. 75
Issue 1
Pg. 62-8
( 1997)
ISSN: 0007-0920 [Print] England |
PMID | 9000599
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents, Alkylating
- Phosphorus Isotopes
- Carbon Dioxide
- Phosphorus
- carbogen
- Oxygen
- Ifosfamide
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Topics |
- Animals
- Antineoplastic Agents, Alkylating
(analysis, pharmacokinetics)
- Carbon Dioxide
(administration & dosage)
- Cell Count
(drug effects)
- Cell Survival
(drug effects)
- Female
- Ifosfamide
(analysis, chemistry, pharmacokinetics)
- Magnetic Resonance Spectroscopy
- Mammary Neoplasms, Animal
(metabolism)
- Oxygen
(administration & dosage)
- Phosphorus
(metabolism)
- Phosphorus Isotopes
- Pituitary Neoplasms
(drug therapy, metabolism)
- Prolactinoma
(drug therapy, metabolism)
- Rats
- Rats, Wistar
- Tumor Cells, Cultured
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