The measurement of radiosensitizer-induced changes in mouse tumor metabolism by 31P magnetic resonance spectroscopy.
Flunarizine and nicotinamide have previously been shown to increase blood perfusion to experimental mouse tumors and consequently, to increase their sensitivity to X rays. These agents were examined for their ability to alter metabolism, measured by 31P magnetic resonance spectroscopy, in the SCCVII/Ha carcinoma and the KHT sarcoma. Flunarizine at 5 mg/kg I.P. produced a 45% reduction in the ratio of inorganic phosphate to total phosphate (Pi/total) in the SCCVII/Ha tumor but only a 24% reduction in this ratio in the KHT tumor. These effects were seen 45 min after drug administration, and ratios returned to control levels by 90 min. In the SCCVII/Ha tumor, nicotinamide at 1000 mg/kg I.P. reduced Pi/total by 56% from 30 min to at least 2 hr after injection, and the ratio was reduced by 59% in the KHT tumor at 30 min after injection, returning to control levels by 2 hr. For the SCCVII/Ha tumor, the time course for the effects of flunarizine and nicotinamide on the inorganic phosphate ratio coincided with that previously reported for radiosensitization.
Wood
P J
PJ
Magnetic Resonance Laboratory, MRC Radiobiology Unit, Chilton, Didcot, Oxon, U.K.
Counsell
C J
CJ
Bremner
J C
JC
Horsman
M R
MR
Adams
G E
GE
D000818:Animals; D002277:Carcinoma / Q000378:metabolism*; D005260:Female; D005444:Flunarizine / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009536:Niacinamide / Q000494:pharmacology*; D010758:Phosphorus; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D012513:Sarcoma, Experimental / Q000378:metabolism*
D011838:Radiation-Sensitizing Agents; D009536:Niacinamide; D010758:Phosphorus; D005444:Flunarizine