脑胶质瘤～（99）Tc～m-HL91显像与其恶性程度之间的关系
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摘要
背景与目的：脑胶质瘤是严重威胁人们生命健康的常见病和多发病。病理学上脑胶质瘤分为高度恶性和低度恶性两种类型，两种胶质瘤虽然在治疗方案的选择上均以手术为主，但术后治疗及病人的预后有很大的不同。CT、MRI、B超等检查方法虽然对脑胶质瘤的定位有很好的价值，但定性价值有待提高；穿刺活检可以定性但只限于肿瘤组织接近颅骨或位于非重要功能部位且具有创伤性，核素显像由于其定性价值而越来越受到重视。脑胶质瘤由于血管结构和功能的异常，导致肿瘤血供减少，加上肿瘤生长迅速，代谢快，耗氧量大，因此肿瘤常处于缺氧状态，乏氧程度越高，恶性程度越重。由于乏氧为肿瘤的一个主要特征，因而应用放射性药物检测组织缺血、缺氧程度，从而鉴别其恶性程度己成为临床研究的一个热点，如应用~(99)Tc~m-HL91进行乏氧显像。近年来国内外进行了大量的动物试验及临床研究，表明~(99)Tc~m-HL91能很好的反映肿瘤乏氧情况，临床上可用于鉴别肿瘤的恶性程度及术后坏死与复发。我们以前的临床研究表明：~(99)To~m-HL91在肺癌的定性诊断中有较高的临床应用价值。本研究拟在临床上对脑胶质瘤患者进行~(99)Tc~m-HL91显像，与手术取得的病理结果进行对照，探讨~(99)Tc~m-HL91在鉴别脑胶质瘤低度恶性和高度恶性方面的价值。
郑州大学医学院2以)4届研究生论文
脑胶质瘤9’T。m一HLgl显像与其恶性程度之间的关系
方法:对24例未经治疗的脑胶质瘤患者进行99Tcm一HLgl三时相
显像:通过患者肘静脉注射99Tem一HLgl 74oMBq(Zomei)(儿童剂量酌
减)，在第10min、Zh和4h进行前后位、后前位和左右侧位平面显像，
配低能高分辨准直器，能峰140keV，窗宽10%。准直器距头部皮肤约
5.ocm，以每帧300秒的方式进行采集，采集矩阵256x256，放大倍数
为1.0一2.0。选取1一2帧肿瘤显像最明显的图像，利用感兴趣区(ROI)
技术，勾画三个同样大小的圆形感兴趣区，在肿瘤显像的三个不同部
位计数，取其均值，记为T;利用计算机的固有程序，在对侧相应部位
产生三个与前者大小、形状相同的ROI，计数，取均值，记为N;计
算不同时相的T/N比值。将显像结果与手术获取的病理结果进行对照，
以判断99Tcm一HLgl在脑胶质瘤定性诊断中的价值。以Zh低度恶性组
的T/N比值牙+ZSD作为判断脑胶质瘤低度恶性和高度恶性的标准，并
计算99Tcm一HLgl显像的灵敏度、特异性和准确率。
结果:
1.病理学结果:24例患者，病理学证实:高度恶性(high malignant
group，HM)17例，低度恶性(low malignant group，LM)7例:19例
”Tcm一HLgl显像阳性的患者中，病理学证实:高度恶性17例，低度恶
性2例。
2.脑胶质瘤”Tcm一H Lgl显像:24例胶质瘤中19例显像阳性，
即在注射示踪剂10min后即可见到肿瘤部位异常放射性浓集，Zh显
像较明显，4h显影较Zh时更明显。体积大且周围组织(如颅骨)影
响小的肿瘤较体积小、且接近颅骨的肿瘤显影清晰。其他患者在10
min一4h期间肿瘤部位未见放射性浓集。
4.肿瘤与正常组织放射性计数的比值(T/N)结果:高度恶性胶
质瘤组10 min、Zh、4h的T/N比值分别为1.775士0.386、1.861士0.388、
1.881士0.434，低度恶性胶质瘤组三时相的T/Nt匕值分别为1.067士0.125、
1.140士0.009、1.110士0.139，各组三时相间T/N比值差异无显著性意义(尸组
内=0 .156，尸>0 .05，双侧)，但低度恶性组和高度恶性组之间差异有显著
性意义(P=0.0006，P<0.001，双侧)。
郑州大学医学院2004届研究生论文
脑胶质瘤99Tcm一IILgl显像与其恶性程度之间的关系
4.”Tcm一HLgl为无色透明液体，多次测定放化纯均>95%。所
有患者注射99Tcm一HLgl后，均未见任何副作用。
5.以大于LM组T/Nt匕值升ZSD即1.158作为判断HM的标准，
则”gTcm一HLgl显像的真阳性为17例，假阳性为2例，真阴性为5例，
假阴性为0例，其诊断的灵敏度、特异性和准确率分别为100%(17/l7)、
7 1 .43%(5/7)、9 1 .67%(22/24)。
结论:
1.99Tcm一HLgl乏氧显像判断脑胶质瘤恶性程度具有较高的灵敏
度和特异性，且无副作用，可作为评价脑胶质瘤恶性程度的方法，T/N
比值可作为判断胶质瘤摄取””Tcm一HLgl的指标。
2.99Tcm一HLgl脑胶质瘤显像以4h最好。
3.gTcm一HLgl显像剂易于配置，是一种潜力很大的乏氧组织显像
剂。
Background and Objective: In these days the brain glioma has become a commonly-seen and frequently-occurred disease that threatening people's life severely. Moreover, glioma can be divided into high grade malignant and low grade malignant in biopsy. Though the treatment method of these two types of glioma is operation mainly, they are different in the postoperative treatment and prognosis. CT, MRI and B supersonic wave have less ability to identify the characters of glioma though they can locate the tumor very well; puncture biopsy can identify the characters of rumor but it is limited to the location of tumors which are apt to approach and in less important position, it also has some injuries to the patients. Nuclide imaging has been taken increasingly attention for its ability of identifying the character of tumor. The brain gliomas, for it s abnormal structure and function of blood vessels ,result in the insufficient blood supply to them.These malignant tumors consume a large quantity of oxygen because gr
owing and metabolizing quickly. So they are usually in hypoxic condition. The more serious hypoxic condition is, the more malignant tumor is. Because hypoxic condition is a main characteristic of tumor, it's a hotspot in clinic research that applying the radiopharmaceutical to detect ischemia and hypoxic condition. Some researchers from home and abroad have done a large number of animal experiments and clinic studies about 99Tcm-HL91 imaging, and they suggested that 99Tcm-HL91 imaging could greatly reflect hypoxia of tumors and tell benign or malignant of rumors and the recurrence or
necrosis of tumors. Our former study indicated that 99Tcm-HL91 imaging can reflect the nature of lung cancer. In this study, we will image gliomas with 99Tcm-HL91 in clinical works, compare the imaging results with histopathological findings, assess the value of 99Tcm-HL91 imaging on identifying the high grade and low grade of malignant gliomas.
Methods: Twenty-four patients with untreated brain gliomas were studied prospectively a week before operation. After intravenous injection of 740 MBq (20mCi) (the dosage of children was reduced relevantly) 99Tcm-HL91 in the arm vein, SPECT images of the head, which including anterior, posterior, left lateral and right lateral planar images, were acquired at 10 minute, 2 hour and 4 hour in all patient after injection by using a single-head gamma camera equipped with low energy, high-resolution parallel-hole collimator. The energy peak was centered at 140 keV and with a 10% window. There are five centimeters between collimator and the patient's head. Data were acquired in a 256x256 matrix and 1.0-2.0 times zoom. The acquisition time is 300 seconds per frame. Images were interpreted visually and semi-quantitatively. One or two images were selected and a round region of interest (ROI) was drawn around the tumor on planar with a same size in three phases and its mean value was calculated, signed as T. The tumor region of interest was mirrored to the contralateral cerebral hemisphere to obtain normal tissue background regions activity and got its' mean value, signed as N. Then we calculated the radioactivity ratios tumour-to-normal tissue (T/N). Based on the MRI and 99Tcm-HL91 SPECT findings, the surgical resection or biopsy was performed. We compared histopathological findings with SPECT imaging results to judge the ability of 99Tcm-HL91 for identifying the character of the tumor. Considering the x+2SD at 2 hours as the standard for judging high or low malignant grade, we assessed malignant gliomas and calculated the sensitivity, specifity and accuracy of this method.
Results:
1. Biopsy results: 17 out of 24 patients were identified as high grade malignant glioma (HM), the other 7 were low grade (LM). 17 out of 19 99Tcm-HL91 positive patients were identified by biopsy as high grade malignant glioma, the remains were low grade.
2. The 99Tcm-HL91 imaging results: In 19 out of 24 99Tcm-HL91 positive patients, injection was concentrated in tumors with a clear imaging at 10min, clearer at 2 h
郑州大学医学院2以)4届研究生论文
脑胶质瘤9’T。m一HLgl显像与其恶性程度之间的关系
方法:对24例未经治疗的脑胶质瘤患者进行99Tcm一HLgl三时相
显像:通过患者肘静脉注射99Tem一HLgl 74oMBq(Zomei)(儿童剂量酌
减)，在第10min、Zh和4h进行前后位、后前位和左右侧位平面显像，
配低能高分辨准直器，能峰140keV，窗宽10%。准直器距头部皮肤约
5.ocm，以每帧300秒的方式进行采集，采集矩阵256x256，放大倍数
为1.0一2.0。选取1一2帧肿瘤显像最明显的图像，利用感兴趣区(ROI)
技术，勾画三个同样大小的圆形感兴趣区，在肿瘤显像的三个不同部
位计数，取其均值，记为T;利用计算机的固有程序，在对侧相应部位
产生三个与前者大小、形状相同的ROI，计数，取均值，记为N;计
算不同时相的T/N比值。将显像结果与手术获取的病理结果进行对照，
以判断99Tcm一HLgl在脑胶质瘤定性诊断中的价值。以Zh低度恶性组
的T/N比值牙+ZSD作为判断脑胶质瘤低度恶性和高度恶性的标准，并
计算99Tcm一HLgl显像的灵敏度、特异性和准确率。
结果:
1.病理学结果:24例患者，病理学证实:高度恶性(high malignant
group，HM)17例，低度恶性(low malignant group，LM)7例:19例
”Tcm一HLgl显像阳性的患者中，病理学证实:高度恶性17例，低度恶
性2例。
2.脑胶质瘤”Tcm一H Lgl显像:24例胶质瘤中19例显像阳性，
即在注射示踪剂10min后即可见到肿瘤部位异常放射性浓集，Zh显
像较明显，4h显影较Zh时更明显。体积大且周围组织(如颅骨)影
响小的肿瘤较体积小、且接近颅骨的肿瘤显影清晰。其他患者在10
min一4h期间肿瘤部位未见放射性浓集。
4.肿瘤与正常组织放射性计数的比值(T/N)结果:高度恶性胶
质瘤组10 min、Zh、4h的T/N比值分别为1.775士0.386、1.861士0.388、
1.881士0.434，低度恶性胶质瘤组三时相的T/Nt匕值分别为1.067士0.125、
1.140士0.009、1.110士0.139，各组三时相间T/N比值差异无显著性意义(尸组
内=0 .156，尸>0 .05，双侧)，但低度恶性组和高度恶性组之间差异有显著
性意义(P=0.0006，P<0.001，双侧)。
郑州大学医学院2004届研究生论文
脑胶质瘤99Tcm一IILgl显像与其恶性程度之间的关系
4.”Tcm一HLgl为无色透明液体，多次测定放化纯均>95%。所
有患者注射99Tcm一HLgl后，均未见任何副作用。
5.以大于LM组T/Nt匕值升ZSD即1.158作为判断HM的标准，
则”gTcm一HLgl显像的真阳性为17例，假阳性为2例，真阴性为5例，
假阴性为0例，其诊断的灵敏度、特异性和准确率分别为100%(17/l7)、
7 1 .43%(5/7)、9 1 .67%(22/24)。
结论:
1.99Tcm一HLgl乏氧显像判断脑胶质瘤恶性程度具有较高的灵敏
度和特异性，且无副作用，可作为评价脑胶质瘤恶性程度的方法，T/N
比值可作为判断胶质瘤摄取””Tcm一HLgl的指标。
2.99Tcm一HLgl脑胶质瘤显像以4h最好。
3.gTcm一HLgl显像剂易于配置，是一种潜力很大的乏氧组织显像
剂。
Background and Objective: In these days the brain glioma has become a commonly-seen and frequently-occurred disease that threatening people's life severely. Moreover, glioma can be divided into high grade malignant and low grade malignant in biopsy. Though the treatment method of these two types of glioma is operation mainly, they are different in the postoperative treatment and prognosis. CT, MRI and B supersonic wave have less ability to identify the characters of glioma though they can locate the tumor very well; puncture biopsy can identify the characters of rumor but it is limited to the location of tumors which are apt to approach and in less important position, it also has some injuries to the patients. Nuclide imaging has been taken increasingly attention for its ability of identifying the character of tumor. The brain gliomas, for it s abnormal structure and function of blood vessels ,result in the insufficient blood supply to them.These malignant tumors consume a large quantity of oxygen because gr
owing and metabolizing quickly. So they are usually in hypoxic condition. The more serious hypoxic condition is, the more malignant tumor is. Because hypoxic condition is a main characteristic of tumor, it's a hotspot in clinic research that applying the radiopharmaceutical to detect ischemia and hypoxic condition. Some researchers from home and abroad have done a large number of animal experiments and clinic studies about 99Tcm-HL91 imaging, and they suggested that 99Tcm-HL91 imaging could greatly reflect hypoxia of tumors and tell benign or malignant of rumors and the recurrence or
necrosis of tumors. Our former study indicated that 99Tcm-HL91 imaging can reflect the nature of lung cancer. In this study, we will image gliomas with 99Tcm-HL91 in clinical works, compare the imaging results with histopathological findings, assess the value of 99Tcm-HL91 imaging on identifying the high grade and low grade of malignant gliomas.
Methods: Twenty-four patients with untreated brain gliomas were studied prospectively a week before operation. After intravenous injection of 740 MBq (20mCi) (the dosage of children was reduced relevantly) 99Tcm-HL91 in the arm vein, SPECT images of the head, which including anterior, posterior, left lateral and right lateral planar images, were acquired at 10 minute, 2 hour and 4 hour in all patient after injection by using a single-head gamma camera equipped with low energy, high-resolution parallel-hole collimator. The energy peak was centered at 140 keV and with a 10% window. There are five centimeters between collimator and the patient's head. Data were acquired in a 256x256 matrix and 1.0-2.0 times zoom. The acquisition time is 300 seconds per frame. Images were interpreted visually and semi-quantitatively. One or two images were selected and a round region of interest (ROI) was drawn around the tumor on planar with a same size in three phases and its mean value was calculated, signed as T. The tumor region of interest was mirrored to the contralateral cerebral hemisphere to obtain normal tissue background regions activity and got its' mean value, signed as N. Then we calculated the radioactivity ratios tumour-to-normal tissue (T/N). Based on the MRI and 99Tcm-HL91 SPECT findings, the surgical resection or biopsy was performed. We compared histopathological findings with SPECT imaging results to judge the ability of 99Tcm-HL91 for identifying the character of the tumor. Considering the x+2SD at 2 hours as the standard for judging high or low malignant grade, we assessed malignant gliomas and calculated the sensitivity, specifity and accuracy of this method.
Results:
1. Biopsy results: 17 out of 24 patients were identified as high grade malignant glioma (HM), the other 7 were low grade (LM). 17 out of 19 99Tcm-HL91 positive patients were identified by biopsy as high grade malignant glioma, the remains were low grade.
2. The 99Tcm-HL91 imaging results: In 19 out of 24 99Tcm-HL91 positive patients, injection was concentrated in tumors with a clear imaging at 10min, clearer at 2 h
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