31P MRS to monitor the induction of tumor hypoxia by the modification of the oxygen affinity of hemoglobin using BW 589C.
OBJECTIVE
BW 589C induces severe tumor hypoxia by modifying the affinity of oxyhemoglobin, causing a left shift of the oxygen-hemoglobin dissociation curve. 31P magnetic resonance spectra (MRS) was used to monitor the effects of BW 589C on tumor energy metabolism in three experimental tumor models.


METHODS
HT-29 colon xenograft, murine transplantable RIF-1 fibrosarcoma and KHT sarcoma were studied in unanesthetised mice. 31P MR spectra were acquired on a 4.7 Tesla magnet before administering oral BW 589C (250 mg/kg) and after 3, 6, and 24 h. Samples of tail vein blood were then taken for 2,3 DPG levels for RIF-1 and HT-29 tumors.


RESULTS
Doubling of inorganic phosphorus (Pi) to total phosphorus was observed 5-6 h after BW 589C for all three tumor types. Although the left shift due to BW 589C persists at 24 h, the level of Pi to total phosphorus returned to baseline with no significant difference from control values for the RIF-1 and HT-29 tumors. These results suggest that there was cellular metabolic adaptation to the reduction of oxygen delivery by BW 589C. This does not appear to involve 2,3 DPG as there was no significant alteration in tumor levels. The death of hypoxic cells may, also, have contributed to the recovery of Pi to total phosphorus.


CONCLUSIONS
The efficacy of bioreductive drugs can be enhanced by increasing the severity of tumor hypoxia. 31P MRS in conjunction with other techniques for assessing the intratumor environment could play an important role in planning cancer therapy.
Kalra
R
R
MRC Radiobiology Unit, Chilton, Didcot, Oxfordshire, UK.
Bremner
J C
JC
Wood
P J
PJ
Sansom
J
J
Counsell
C J
CJ
Stratford
I J
IJ
Adams
G E
GE
D000818:Animals; D001547:Benzaldehydes / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects*; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*
D001547:Benzaldehydes; D001565:Benzoates; D006454:Hemoglobins; C059629:tucaresol; D010100:Oxygen