MEASURING PO2 IN BEATING RAT HEART

测量跳动的大鼠心脏中的 PO2

• 批准号: 6353175
• 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: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2002-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6353175
• 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 通过将放射性元素与抗体连接到肿瘤 在肿瘤中积聚并保留在肿瘤组织中许多时间 天，从而在一个连续的低剂量辐射 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，以改善 结果并确定为什么某些肿瘤无法通过 治疗。 放射性抗体位于血液附近的肿瘤中 血管并可能导致血管功能的变化 影响瘤内 pH 值和 pO2 以及瘤内间质 压力。 这些变化的净效应可能不仅会影响 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 （例如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 pO2 的影响。 低 pO2 可能意味着肿瘤对辐射不太敏感，而且 由于血液受损，药物治疗可能不太容易 供应。 干预方法可能会导致更合适的结果 针对个别肿瘤的治疗。 电子顺磁共振 (EPR) 植入肿瘤的固体顺磁材料的血氧测定法将 用于监测长期辐射传递过程中的 pO2 确定肿瘤氧合作用在这种新形式期间是否发生变化 的放射治疗。 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 侧翼 s.c，包括 GW-39、LS174T、HT-29 和 GS-7 人类结肠 癌或 ME-180 人宫颈癌或 CALU-3 非小 细胞肺腺癌。 肿瘤将被植入顺磁性 材料，在一个部位 400 微米的 Glooxy，或 25 微升的 无菌顺磁材料浆料。 植入此后 材料中，将使用 EPR 监测肿瘤中的 pO2。 24 第一次 pO2 测量后数小时，将给小鼠注射 放射性 I-131 完整 IgG（约 100-200 微升）腹膜内注射I-131 是 将能量沉积在 1 毫米范围内的放射性核素。 然后氧分压 前 72 小时和第 7 天左右每天都会进行监测 此后的时间间隔在实验期间。