A comparison of the physiological effects of RSU1069 and RB6145 in the SCCVII murine tumour.
The physiological and therapeutic effects of the bioreductive agent RSU1069 (80 mg/kg i.p.) and its prodrug RB6145 (240 mg/kg i.p.) were investigated in the SCCVII tumour. Using laser Doppler flowmetry it was found that RSU1069 produced a significant 30% reduction in tumour blood flow 30 min after administration, while RB6145 had no effect. Tumour oxygenation, measured with an Eppendorf oxygen electrode, was unchanged by either agent except for a reduction in values less than 2.5 mmHg at 30 min after injection. Neither agent significantly altered tumour energy metabolism, assessed by 31P magnetic resonance spectroscopy. Both agents significantly increased tumour glucose content by a factor of 1.6-1.7 at 30 min after injection, but had no effect on glucose-6-phosphate or lactate levels. Tumour growth was significantly delayed by heating (42.5 degrees C, 60 min), and although neither RSU1069 nor RB6145 alone had any effect on tumour growth they produced a similar enhancement of the tumour response to heat. The therapeutic effects are consistent with the known conversion in vivo of one third of the pro-drug RB6145 to its active product RSU1069, however the physiological effects of the two agents in the SCCVII tumour are not identical.
Wood
P J
PJ
MRC Radiobiology Unit, Chilton, Didcot, Oxon, UK.
Horsman
M R
MR
Khalil
A A
AA
Steinberg
F
F
Streffer
C
C
Overgaard
J
J
Stratford
I J
IJ
Adams
G E
GE
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008920:Misonidazole / Q000031:analogs & derivatives* / Q000494:pharmacology; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D009593:Nitroimidazoles / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism*; D010761:Phosphorus Radioisotopes
D000970:Antineoplastic Agents; D009593:Nitroimidazoles; D010761:Phosphorus Radioisotopes; C067834:RB 6145; C041712:1-(2-nitro-1-imidazolyl)-3-aziridino-2-propanol; D008920:Misonidazole; D010100:Oxygen