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极谱氧测定法、对比增强彩色双功超声检查(CDS)、[18F]氟米索硝唑和[18F]氟脱氧葡萄糖正电子发射断层扫描:评估与治疗相关的肿瘤氧合的有效方法,还是仅仅是肿瘤缺氧难题中的几块拼图?

pO polarography, contrast enhanced color duplex sonography (CDS), [18F] fluoromisonidazole and [18F] fluorodeoxyglucose positron emission tomography: validated methods for the evaluation of therapy-relevant tumor oxygenation or only bricks in the puzzle of tumor hypoxia?

作者信息

Gagel Bernd, Piroth Marc, Pinkawa Michael, Reinartz Patrick, Zimny Michael, Kaiser Hans J, Stanzel Sven, Asadpour Branka, Demirel Cengiz, Hamacher Kurt, Coenen Heinz H, Scholbach Thomas, Maneschi Payam, DiMartino Ercole, Eble Michael J

机构信息

Department of Radiotherapy, RWTH Aachen University, Germany.

出版信息

BMC Cancer. 2007 Jun 28;7:113. doi: 10.1186/1471-2407-7-113.

Abstract

BACKGROUND

The present study was conducted to analyze the value of ([18F] fluoromisonidazole (FMISO) and [18F]-2-fluoro-2'-deoxyglucose (FDG) PET as well as color pixel density (CPD) and tumor perfusion (TP) assessed by color duplex sonography (CDS) for determination of therapeutic relevant hypoxia. As a standard for measuring tissue oxygenation in human tumors, the invasive, computerized polarographic needle electrode system (pO2 histography) was used for comparing the different non invasive measurements.

METHODS

Until now a total of 38 Patients with malignancies of the head and neck were examined. Tumor tissue pO2 was measured using a pO2-histograph. The needle electrode was placed CT-controlled in the tumor without general or local anesthesia. To assess the biological and clinical relevance of oxygenation measurement, the relative frequency of pO2 readings, with values < or = 2.5, < or = 5.0 and < or = 10.0 mmHg, as well as mean and median pO2 were stated. FMISO PET consisted of one static scan of the relevant region, performed 120 min after intravenous administration. FMISO tumor to muscle ratios (FMISOT/M) and tumor to blood ratios (FMISOT/B) were calculated. FDG PET of the lymph node metastases was performed 71 +/- 17 min after intravenous administration. To visualize as many vessels as possible by CDS, a contrast enhancer (Levovist, Schering Corp., Germany) was administered. Color pixel density (CPD) was defined as the ratio of colored to grey pixels in a region of interest. From CDS signals two parameters were extracted: color hue--defining velocity (v) and color area--defining perfused area (A). Signal intensity as a measure of tissue perfusion (TP) was quantified as follows: TP = vmean x Amean.

RESULTS

In order to investigate the degree of linear association, we calculated the Pearson correlation coefficient. Slight (|r| > 0.4) to moderate (|r| > 0.6) correlation was found between the parameters of pO2 polarography (pO2 readings with values < or = 2.5, < or = 5.0 and < or = 10.0 mmHg, as well as median pO2), CPD and FMISOT/M. Only a slight correlation between TP and the fraction of pO2 values < or = 10.0 mmHg, median and mean pO2 could be detected. After exclusion of four outliers the absolute values of the Pearson correlation coefficients increased clearly. There was no relevant association between mean or maximum FDG uptake and the different polarographic- as well as the CDS parameters.

CONCLUSION

CDS and FMISO PET represent different approaches for estimation of therapy relevant tumor hypoxia. Each of these approaches is methodologically limited, making evaluation of clinical potential in prospective studies necessary.

摘要

背景

本研究旨在分析[18F]氟米索硝唑(FMISO)和[18F]-2-氟-2'-脱氧葡萄糖(FDG)PET以及彩色双功超声(CDS)评估的彩色像素密度(CPD)和肿瘤灌注(TP)在确定与治疗相关的缺氧情况中的价值。作为测量人类肿瘤组织氧合的标准,采用侵入性计算机化极谱针电极系统(pO2组织成像)来比较不同的非侵入性测量方法。

方法

截至目前,共对38例头颈部恶性肿瘤患者进行了检查。使用pO2组织成像仪测量肿瘤组织的pO2。在CT引导下,无需全身或局部麻醉,将针电极置于肿瘤内。为评估氧合测量的生物学和临床相关性,列出了pO2读数<或=2.5、<或=5.0和<或=10.0 mmHg时的相对频率以及平均和中位数pO2。FMISO PET包括在静脉注射后120分钟对相关区域进行一次静态扫描。计算FMISO肿瘤与肌肉比值(FMISOT/M)和肿瘤与血液比值(FMISOT/B)。静脉注射后71±17分钟对淋巴结转移灶进行FDG PET检查。为通过CDS尽可能多地显示血管,给予了一种造影剂(德国先灵公司的Levovist)。彩色像素密度(CPD)定义为感兴趣区域中彩色像素与灰色像素的比值。从CDS信号中提取了两个参数:色彩色调——定义速度(v)和色彩面积——定义灌注面积(A)。作为组织灌注(TP)测量指标的信号强度按以下方式量化:TP = v平均×A平均。

结果

为研究线性关联程度,我们计算了Pearson相关系数。在pO2极谱法参数(pO2读数<或=2.5、<或=5.0和<或=10.0 mmHg以及中位数pO2)、CPD和FMISOT/M之间发现了轻度(|r|>0.4)至中度(|r|>0.6)的相关性。仅在TP与pO2值<或=10.0 mmHg的比例、中位数和平均pO2之间检测到轻度相关性。排除四个异常值后,Pearson相关系数的绝对值明显增加。平均或最大FDG摄取与不同的极谱法以及CDS参数之间没有相关关联。

结论

CDS和FMISO PET代表了评估与治疗相关的肿瘤缺氧的不同方法。这些方法在方法学上都有局限性,因此有必要在前瞻性研究中评估其临床潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5000/1948005/992adf2d0243/1471-2407-7-113-1.jpg

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