In vivo evaluation of percutaneous carbon dioxide treatment for improving intratumoral hypoxia using ¹⁸F-fluoromisonidazole PET-CT

Carbon dioxide (CO₂) treatment is reported to have an antitumor effect owing to the improvement in intratumoral hypoxia. Previous studies were based on histological analysis alone. In the present study, the improvement in intratumoral hypoxia by percutaneous CO₂ treatment in vivo was determined using ¹⁸F-fluoromisonidazole positron emission tomography-computed tomography (¹⁸F-FMISO PET-CT) images. Twelve Japanese nude mice underwent implantation of LM8 tumor cells in the dorsal subcutaneous area 2 weeks before percutaneous CO₂ treatment and ¹⁸F-FMISO PET-CT scans. Immediately after intravenous injection of ¹⁸F-FMISO, CO₂ and room air were administered transcutaneously in the CO₂-treated group (n=6) and a control group (n=6), respectively; each treatment was performed for 10 minutes. PET-CT was performed 2 h after administration of ¹⁸F-FMISO. ¹⁸F-FMISO tumor uptake was quantitatively evaluated using the maximum standardized uptake value (SUV_max), tumor-to-liver ratio (TLR), tumor-to-muscle ratio (TMR), metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Mean ± standard error of the mean (SEM) of the tumor volume was not significantly different between the two groups (CO₂-treated group, 1.178±0.450 cm³; control group, 1.368±0.295 cm3; P=0.485). Mean ± SEM of SUV_max, TLR, MTV (cm3) and TLG were significantly lower in the CO₂-treated group compared with the control group (0.880±0.095 vs. 1.253±0.071, P=0.015; 1.063±0.147361 vs. 1.455±0.078, P=0.041; 0.353±0.139 vs. 1.569±0.438, P=0.015; 0.182±0.070 vs. 1.028±0.338, P=0.015), respectively. TMR was not significantly different between the two groups (4.520±0.503 vs. 5.504±0.310; P=0.240). In conclusion, ¹⁸F-FMISO PET revealed that percutaneous CO₂ treatment improved intratumoral hypoxia in vivo. This technique enables assessment of the therapeutic effect in CO₂ treatment by imaging, and may contribute to its clinical application.