phosphorus-radioisotopes and carbogen

Interstitial irradiation therapy using radionuclides is a slow and continual process in which the effect is exerted gradually, thus improvement of the hypoxic status of the tumor will also take a long time. It has been known that carbogen delivery of 5-15 min increases tumor oxygenation. However, the long-term effect of carbogen breathing on hypoxic cells has not yet been determined, and little is know about the effect of carbogen breathing for sensitization to interstitial irradiation therapy.. 99mTc-HL91(99mTc 4,9-diaza-3,3,10,10-tetramethyldodecan-2,1-dione dioxime) hypoxic imaging was performed in 10 mice bearing sarcoma 180 (S180) before and after 2 h carbogen breathing. Radioactivity ratios of tumor to contralateral limbs (T/L) of the 2 images were calculated and compared. Mice bearing S180 were subjected to long-term carbogen breathing (2 h/day for 24 days), and were treated with or without 32P-colloid. Tumor growth rate was observed in the S180-bearing mice.. T/L of 99mTc-HL91 uptake before and after carbogen breathing was 1.872+/-0.391 and 1.354+/-0.189, respectively (t=4.476, P<0.01). In mice in the 32P-treated air breathing group and 32P-treated carbogen breathing group, tumor growth rate did not differ on day 12 after 32P-colloid treatment, and on day 24 the tumor volume was 2.728+/-0.469 and 2.237+/-0.603 cm3 (t=2.128, P<0.05), respectively, with tumor mass being 2.437+/-0.447 and 1.965+/-0.538 g (t=2.134, P<0.05), respectively.. Long-term carbogen breathing can increase tumor oxygenation and continual carbogen breathing is necessary for enhancing the therapeutic effect of 32P-colloid interstitial irradiation.

Topics: Animals; Brachytherapy; Carbon Dioxide; Cell Hypoxia; Mice; Mice, Inbred BALB C; Organotechnetium Compounds; Oximes; Oxygen; Phosphorus Radioisotopes; Radiation-Sensitizing Agents; Sarcoma 180

For the systemic treatment of colorectal cancer, 5-fluorouracil (FU)-based chemotherapy is the standard. However, only a subset of patients responds to chemotherapy. Breathing of carbogen (95% O2 and 5% CO2) may increase the uptake of FU through changes in tumor physiology. This study aims to monitor in animal models in vivo the effects of carbogen breathing on tumor blood plasma volume, pH, and energy status, and on FU uptake and metabolism in two colon tumor models C38 and C26a, which differ in their vascular structure and hypoxic status. Phosphorus-31 magnetic resonance spectroscopy (MRS) was used to assess tumor pH and energy status, and fluorine-19 MRS was used to follow FU uptake and metabolism. Advanced magnetic resonance imaging methods using ultrasmall particles of iron oxide were performed to assess blood plasma volume. The results showed that carbogen breathing significantly decreased extracellular pH and increased tumor blood plasma volume and FU uptake in tumors. These effects were most significant in the C38 tumor line, which has the largest relative vascular area. In the C26a tumor line, carbogen breathing increased tumor growth delay by FU. In this study, carbogen breathing also enhanced systemic toxicity by FU.

Topics: Animals; Antimetabolites, Antineoplastic; Carbon Dioxide; Cell Line, Tumor; Colonic Neoplasms; Disease Models, Animal; Fluorine Radioisotopes; Fluorouracil; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Neovascularization, Pathologic; Oxygen; Phosphorus Radioisotopes; Plasma; Radiation-Sensitizing Agents; Respiration