Previously, (31)P magnetic resonance spectroscopy (MRS) has been used to detect
ifosfamide (IF) in vivo and to show that breathing
carbogen (5% CO(2)/95% O(2)) enhances the uptake and increases the efficacy of IF in rat GH3
prolactinomas [Rodrigues LM, Maxwell RJ, McSheehy PMJ, Pinkerton CR, Robinson SP, Stubbs M, and Griffiths JR (1997). In vivo detection of
ifosfamide by (31)P MRS in rat tumours; increased uptake and cytotoxicity induced by
carbogen breathing in GH3
prolactinomas. Br J
Cancer 75, 62-68]. We now show that other hypercapnic and/or hyperoxic (5% CO(2) in air, 2.5% CO(2) in O(2)) gas mixtures also increase the uptake of IF into
tumors, measured by (31)P MRS. All
gases caused an increased uptake (C(max)) of IF compared to air breathing, with
carbogen inducing the largest increase (85% (P<.02) compared to 46% with 2.5% CO(2) in O(2) (P<.004) and 48% with 5% CO(2) in air (P<.004)). The T(max) (time of maximum concentration in
tumor posintravenous injection of IF) was significantly (P<.04) later in the cohort that breathed 5% CO(2) in air. The increased uptake of IF with
carbogen breathing was selective to
tumor tissue and there were no significant increases in any of the normal tissues studied, suggesting that any host tissue toxicity would be minimal.
Carbogen breathing by patients causes
breathlessness. There was no significant difference in IF uptake between breathing
carbogen and 2.5% CO(2) in O(2) and, therefore, the ability of 2.5% CO(2) in O(2) to also increase IF uptake may be clinically useful as it causes less patient discomfort.