Analysis of tumor reoxygenation using ^<31>P-MRS and hypoxic cell imaging

使用^ 31 P-MRS和缺氧细胞成像分析肿瘤再氧合

• 批准号: 13670918
• 负责人: SAKURAI Hideyuki
• 金额: $ 2.24万
• 依托单位: Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670918/
• 关键词: hypoxic cell; tumor; radiation; reoxygenation; MR spectroscopy; ^<31>P-MRS; HIF-1; MR Spectroscopy

Tumor hypoxic status causes not only radioresistance but also malignant progression such as metastasis,tissue invasion of the tumor. Non-invasive measurement of tumor hypoxia is available for establishing individualization of the cancer treatment.(1) The amount of hypoxic fraction in a rodent tumor was evaluated by polarographic oxygen electrode, ^31P-MRS, and a newly synthesized hypoxic marker, β-D-IAZGP. We also investigated the relationship between the radiosensrtivity of the tumor and the hypoxic fraction predicted by these 3 methods. Radiosensitivity of the tumor was measured by in vivo/in vitro clonogenic assay. Tumor oxygenation status was also measured directly by polarographic oxygen electrodes and indirectly estimated by ^<31>P-MRS. Higher accumulaion of ^<123>I-β-D-IAZGP was observed in the tumors than that in normal tissues at 24hr after administration. As to biodistribution of ^<125>I-β-D-IAGP,the tumor/blood ratio varted widely, but it was correlated with tumor weight. Me … More an p_O_2 values and β-ATP/Pi, PCr/Pi ratios decreased significantly with the increase in tumor volume. As tumor volume increased, tumor cells became more resistant to radiation. The increase in tumor volume was significantly ccirelated with the recbction in mean p_O_2, decrease in ratios ofβATP/Pi or PCr/Pi, increase in uptake of β-D-IAZGP and redioresistance. Because the uptake of β-D-IAZGP can be measured non-invasively by nuclear medicine techniques, it could be clinically useful for monitoring hypoxia in human tumors.(2) To clarify a correlation between tumor hypoxia and malignant progression, we examined an expression of HIF-1 in the tumor of the stage III uterine cervix cancer. Five-year disease free survival rates were 41.2 % in HIF-1 positive group and 75.6% in HIF-1 negative group with statistical significance. Because strong correlation in distant metastasis was found between HIF-1 positive and negative group, the expression of HIF-1 showed malignant progression of the tumor in the uterine cervix. Less

肿瘤缺氧状态不仅导致放射抵抗，而且导致恶性进展，如肿瘤的转移、组织浸润。肿瘤缺氧的非侵入性测量可用于建立癌症治疗的个体化。(1)用极谱氧电极、~（31）P-MRS和新合成的缺氧标记物β-D-IAZGP来评估啮齿动物肿瘤中缺氧组分的量。我们还研究了肿瘤的放射敏感性与这三种方法预测的乏氧分数之间的关系。采用体内/体外克隆形成试验测定肿瘤的放射敏感性。用极谱氧电极直接测定肿瘤氧合状态，用~ 13 P-MRS间接评价肿瘤氧合状态<31>，<123>给药后24小时肿瘤组织中~ 13 I-β-D-IAZGP的蓄积量明显高于正常组织。β-D-IAGP的生物分布<125>与肿瘤重量有关，瘤/血比值变化较大。我 ...更多信息 p_O_2值和β-ATP/Pi、PCr/Pi比值随肿瘤体积的增大而显著降低。随着肿瘤体积的增加，肿瘤细胞对辐射的抵抗力也越来越强。肿瘤体积的增大与平均p_O_2下降、βATP/Pi或PCr/Pi比值下降、β-D-IAZGP摄取增加及放射抵抗性增加密切相关。由于β-D-IAZGP的摄取可以通过核医学技术非侵入性地测量，因此它可能在临床上用于监测人类肿瘤中的缺氧。(2)为了阐明肿瘤缺氧与恶性进展之间的相关性，我们检测了III期宫颈癌肿瘤中HIF-1的表达。HIF-1阳性组5年无瘤生存率为41.2%，HIF-1阴性组为75.6%，差异有统计学意义。由于HIF-1阳性组与阴性组之间的远处转移有很强的相关性，HIF-1的表达提示宫颈癌的恶性进展。少

项目成果

Imai R: "Small cell lung cancer with a brain metastasis controlled for 5 years : a case report"Jpn J Clin Oncol. 31. 116-118 (2001)

Imai R：“小细胞肺癌脑转移得到控制 5 年：病例报告”Jpn J Clin Oncol。

Sakurai H: "A challenge for Non-small cell lung cancer using hyperthemia"Jpn. J Hyperthennic Oncol. 171. 23-31 (2001)

Sakurai H：“利用热疗治疗非小细胞肺癌的挑战”Jpn。

Islam MS, Sakurai H et al.: "Hyperthetmia-induced apoptosis in two rat yolk sac tumor cell lines with different radiothermosensitivity in vitro"Oncol Rep. 8. 501-407 (2001)

Islam MS、Sakurai H 等人：“体外具有不同放射热敏感性的两种大鼠卵黄囊肿瘤细胞系中的Hyperthetmia-induced 细胞凋亡”Oncol Rep. 8. 501-407 (2001)

Imai R, Sakurai H et al.: "Small cell lung cancer with a brain metastasis controlled for 5 years : a case report"Jpn J Chn Oncol. 31. 116-118 (2001)

Imai R、Sakurai H 等：“小细胞肺癌脑转移控制 5 年：病例报告”Jpn J Chn Oncol。

Sakurai H: "Analysis of recurrence of squamous cell carcinoma of the uterine cervix after definitive radiation therapy alone -patterns of recurrence, latent periods and prognosis"Int.J.Radiat.Oncol.Biol.Phys.. 50・5. 1136-1144 (2001)

Sakurai H：“单纯放射治疗后宫颈鳞状细胞癌复发的分析 - 复发模式、潜伏期和预后”Int.J.Radiat.Oncol.Biol.Phys. 50・5。 (2001)