MEASURING PO2 IN BEATING RAT HEART

据报道，有几种人类肿瘤可以控制肿瘤生长。 异种移植模型及几项放射性临床试验 通过将放射性元素与抗体连接而传递给肿瘤 在肿瘤中积聚，并在肿瘤组织中保留许多年 天，从而在一年内提供持续的低剂量辐射 癌症治疗称为放射免疫疗法(RAIT)。有必要 了解RAIT对肿瘤生理学的影响，以期改善 结果，并确定为什么一些肿瘤无法通过 心理治疗。放射性抗体定位在靠近血液的肿瘤中。 并可能引起血管功能的改变，可能 对瘤内pH、PO2及瘤内间质的影响 压力。这些变化的净影响可能不仅影响到 在多个周期内累积额外剂量的放射抗体 方案，但也可能影响其他抗肿瘤药物的吸收 (例如，药物或生物反应调节剂)。在这项研究中，我们 探讨低剂量率照射对肿瘤氧分压的影响。 低氧分压可能意味着肿瘤对辐射不那么敏感，而且 由于血液受损，可能更难获得药物治疗 供给。干预的方法可能会导致更合适的 针对个别肿瘤的治疗。电子顺磁共振(EPR) 肿瘤内植入固体顺磁性材料的血氧测定法 用于监测PO2对辐射的长期传输 确定在这种新形式下肿瘤的氧合是否发生变化 关于放射治疗的问题。被研究的动物是裸鼠(T细胞 有缺陷的)携带六种不同的人肿瘤异种移植瘤中的一种 侧翼S.C.包括GW-39、LS174T、HT-29和GS-7人结肠 人宫颈癌或ME-180癌或CALU-3非小细胞癌 细胞性肺腺癌。肿瘤将被植入顺磁性 材料，一个部位400微米的玻璃，或25微升的 无菌顺磁材料制成的浆料。在植入这个之后 材料，PO2将使用EPR在肿瘤中进行监测。二十四 在第一次PO2测量数小时后，小鼠将被注射 放射性~(131)I-完整免疫球蛋白(~100-200微升)I.P.I-131是一种 在1毫米范围内储存能量的放射性核素。然后是PO2 将在最初72小时和大约7天内每天进行监测 在此之后的间隔时间为实验持续时间。

Control of tumor growth has been reported for several human tumor xenograft models and for a few clinical trials using radioactivity delivered to tumors by linking a radioactive element to an antibody that accumulates in tumor and is retained in tumor tissue for many days, thereby delivering a continuous low dose of radiation in a cancer treatment called Radioimmunotherapy (RAIT). There is a need to understand the effects of RAIT on tumor physiology in order to improve results and to determine why some tumors fail to be controlled by the therapy. The radio-antibodies localize in the tumor near the blood vessels and possibly cause changes in vascular function that may influence intratumoral pH and pO2 and intratumoral interstitial pressure. The net effect of these changes may not only impact on the accumulation of additional doses of radioantibody in a multiple cycle scheme, but may also influence the uptake of other anti-tumor agents (e.g. drugs, or biological response modifiers). In this study we are investigating the effects of low-dose rate radiation on tumor pO2. Low pO2 could mean a tumor is less sensitive to radiation and also potentially less accessible to drug therapy due to a damaged blood supply. Methods to intervene could then result in a more appropriate therapy for individual tumors. Electron paramagnetic resonance (EPR) oximetry with solid paramagnetic materials implanted in the tumor will be used to monitor pO2 over the long term delivery of radiation to determine whether the tumor oxygenation changes during this new form of radiation therapy. Animals to be studied are Nude mice (T-cell deficient) bearing one of six different human tumor xenografts grown s.c on the flank including GW-39, LS174T, HT-29 and GS-7 human colonic carcinomas or ME-180 human cervical carcinoma or the CALU- 3 non-small cell lung adenocarcinoma. Tumors will be implanted with paramagnetic material, 400 um piece of gloxy at one site, or 25 microliters of a slurry of sterile paramagnetic material. After implantation of this material, pO2 will be monitored in the tumor using EPR. Twenty four hours after the first pO2 measurement, mice will be injected with radioactive I-131-intact IgG (~100-200microliters) i.p. I-131 is a radionuclide that deposits its energy within a 1-mm range. Then pO2 will be monitored daily for the first 72 hrs and at about 7 day intervals after that for the duration of the experiment.