MEASURING PO2 IN BEATING RAT HEART

测量跳动的大鼠心脏中的 PO2

• 批准号: 6206501
• 负责人: Oleg Grinberg
• 金额: $ 1.22万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6206501
• 关键词: Mammalia; bioengineering /biomedical engineering; biomedical resource; gas; neoplasm /cancer; radiology; technology /technique

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.

已经报道了几种人类肿瘤的肿瘤生长控制 异种移植模型和一些使用放射性的临床试验 通过将放射性元素连接到抗体上来输送到肿瘤中 在肿瘤中积累，并保留在肿瘤组织中， 天，从而提供了一个连续的低剂量的辐射， 放射免疫疗法（赖特）。 有必要 了解赖特对肿瘤生理学的影响，以改善 结果，并确定为什么一些肿瘤不能被控制的 疗法 放射性抗体定位于肿瘤内靠近血液的地方 血管，并可能导致血管功能的变化， 影响肿瘤内pH和pO 2以及肿瘤内间质 压力 这些变化的净效应可能不仅影响 在多个周期中累积额外剂量的放射性抗体 方案，但也可能影响其他抗肿瘤药物的摄取 (e.g.药物或生物反应调节剂）。 在这项研究中，我们 研究低剂量率辐射对肿瘤pO 2的影响。 低pO 2可能意味着肿瘤对辐射不太敏感， 由于受损的血液， 供应 干预的方法可能会导致更适当的 治疗个别肿瘤。 电子顺磁共振（EPR） 在肿瘤中植入固体顺磁性材料的血氧测定法将 用于监测长期辐射输送过程中的pO 2， 确定肿瘤氧合是否在这种新形式的过程中发生变化， 放射治疗 待研究的动物是裸鼠（T细胞 缺陷）携带六种不同的人类肿瘤异种移植物之一， 侧腹皮下注射，包括GW-39、LS 174 T、HT-29和GS-7人结肠 癌或ME-180人宫颈癌或CALU- 3非小细胞癌 肺腺癌 肿瘤将植入顺磁性 材料，在一个位点处的400 μ m的gloxy片，或25微升的 无菌顺磁材料的浆液。 在植入这个 材料，将使用EPR监测肿瘤中的pO 2。 二十四 在第一次pO 2测量后24小时，将向小鼠注射 放射性I-131-完整IgG（~100- 200微升）i. p. I-131是一种 在1毫米范围内沉积其能量的放射性核素。 然后是pO 2 将在前72小时和第7天左右每天进行监测 在实验的持续时间之后的时间间隔。