Effects of different levels of hypercapnic hyperoxia on tumour R-2* and arterial blood gases

The hypercapnia induced by carbogen (95% O-2/5% CO2) breathing, which is be ing re-evaluated as a clinical radiosensitiser, causes patient discomfort a nd hence poor compliance. Recent preclinical and clinical studies have indi cated that the CO2 content might be lowered without compromising increased tumour oxygenation and radiosensitisation. This preclinical study was desig ned to see if lower levels of hypercapnia could evoke similar decreases in the transverse relaxation rate R-2* of rodent rumours to those seen with ca rbogen breathing. The response of rat GH3 prolactinomas to 1%, 2 1/2% and 5 % CO2 in oxygen, and 100% O-2 breathing, was monitored by non-invasive mult i-gradient echo MRI to quantify R-2*. As the oxygenation of haemoglobin is proportional to the blood p(a)O(2) and therefore in equilibrium with tissue pO(2), R-2* is a sensitive indicator of tissue oxygenation. Hyperoxia alon e decreased R-2* by 13%, whilst all three hypercapnic hyperoxic gases decre ased R-2* by 29%. Breathing 1% CO2 in oxygen evoked the same decrease in R- 2* as carbogen. The DeltaR(2)* response is primarily consistent with an inc rease in blood oxygenation, though localised increases in tumour blood flow were also identified in response to hypercapnia. The data support the conc ept that levels of hypercapnia can be reduced without loss of enhanced oxyg enation and hence potential radiotherapeutic benefit. (C) 2001 Elsevier Sci ence Inc. All rights reserved.