Effects of different levels of hypercapnic hyperoxia on tumour R2∗ and arterial blood gases

The hypercapnia induced by carbogen (95% O2/5% CO2) breathing, which is being re-evaluated as a clinical radiosensitiser, causes patient discomfort and hence poor compliance. Recent preclinical and clinical studies have indicated that the CO2 content might be lowered without compromising increased tumour oxygenation and radiosensitisation. This preclinical study was designed to see if lower levels of hypercapnia could evoke similar decreases in the transverse relaxation rate R2∗ of rodent tumours to those seen with carbogen breathing. The response of rat GH3 prolactinomas to 1%, 212% and 5% CO2 in oxygen, and 100% O2 breathing, was monitored by non-invasive multi-gradient echo MRI to quantify R2∗. As the oxygenation of haemoglobin is proportional to the blood paO2 and therefore in equilibrium with tissue pO2, R2∗ is a sensitive indicator of tissue oxygenation. Hyperoxia alone decreased R2∗ by 13%, whilst all three hypercapnic hyperoxic gases decreased R2∗ by 29%. Breathing 1% CO2 in oxygen evoked the same decrease in R2∗ as carbogen. The ΔR2∗ response is primarily consistent with an increase in blood oxygenation, though localised increases in tumour blood flow were also identified in response to hypercapnia. The data support the concept that levels of hypercapnia can be reduced without loss of enhanced oxygenation and hence potential radiotherapeutic benefit.