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99mTc-MIBI与201T1肺肿瘤阳性显像在原发性肺癌的比较
http://www.100md.com 《中山大学学报(医学科学版)》 2000年第1期
     作者:梁宏 陈小可 胡平 李伟明 曾世荃 饶国辉 岳殿超 陈维安 吴克宁 李春亿

    单位:中山医科大学附属第一医院 核医学科 广东 广州 510080

    关键词:肺肿瘤;放射性核素显像;肺肿瘤;诊断;甲氧异腈;铊

    中山医科大学学报000115摘 要:目的 评价99mTc-MIBI与201T1肺肿瘤显像在原发性肺癌诊断中临床意义。方法 28例肺癌患者进行了201T1早期(15 min)与延迟(3 h)肺肿瘤平面显像,其中23例有同期的99mTc-MIBI显像资料;勾画各时相前位图像上病变部位(T)及对侧正常肺组织(N)的感兴趣区,计算摄取比值(T/N)及滞留指数[RI=(延迟T/N-早期T/N)×100/早期T/N)],并取病灶部位放射性较正常肺组织摄取明显增高为阳性指标进行定性分析。结果 99m Tc-MIBI早期与延迟显像肉眼定性分析诊断肺癌的阳性率分别为86.96%和78.26%,201T1显像两者阳性率均为89.29%;99mTc-MIBI早期与延迟显像T/N分别为1.26±0.19与1.24±0.19,201T1为1.43±0.21和1.59±0.32,99mTc-MIBI与201T1比较早期T/N之间与延迟T/N之间均有明显差异(t值分别为5.538与7.33,P值均<0.001);同时201T1显像所计算的滞留指数(10.83±11.80)%明显大于99mTc-MIBI肺显像(-1.44±6.62)%,差异有显著意义(t=4.307,P<0.001)。结论 99m Tc-MIBI与201T1肺显像在原发性肺癌的诊断中具有较高的阳性预测值,但肿瘤部位的滞留指数后者明显增高,提示201T1肺显像更具优越性,对于两者在肺癌淋巴结转移灶探测中的临床价值,有待更深入研究。
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    分类号:R 816.41; R 734.2 文献标识码:A

    文章编号:1000-257X(2000)01-0050-04

    The Comparisom of Technetium-99m-MIBI and Thallium-201 Lung

    Scintigraphy in Primary Lung Cancer

    LIANG Hong

    (Department of Nuclear Medicine Department of Internal Medicine, First Affiliated Hospital Sun Yat-sen University of Medical Sciences, Guangzhou, 510080,China)
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    CHEN Xiao-ke

    (Devision of Respiratory, Department of Internal Medicine, First Affiliated Hospital Sun Yat-sen University of Medical Sciences, Guangzhou, 510080,China)

    HU Ping

    (Department of Nuclear Medicine Department of Internal Medicine, First Affiliated Hospital Sun Yat-sen University of Medical Sciences, Guangzhou, 510080,China)

    LI Wei-ming
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    (Department of Nuclear Medicine Department of Internal Medicine, First Affiliated Hospital Sun Yat-sen University of Medical Sciences, Guangzhou, 510080,China)

    ZENG Shi-quna

    (Department of Nuclear Medicine Department of Internal Medicine, First Affiliated Hospital Sun Yat-sen University of Medical Sciences, Guangzhou, 510080,China)

    RAO Guo-hui

    (Department of Nuclear Medicine Department of Internal Medicine, First Affiliated Hospital Sun Yat-sen University of Medical Sciences, Guangzhou, 510080,China)
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    YUE Dian-chao

    (Department of Nuclear Medicine Department of Internal Medicine, First Affiliated Hospital Sun Yat-sen University of Medical Sciences, Guangzhou, 510080,China)

    CHEN Wei-an

    (Department of Nuclear Medicine Department of Internal Medicine, First Affiliated Hospital Sun Yat-sen University of Medical Sciences, Guangzhou, 510080,China)

    WU Ke-ning
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    (Department of Nuclear Medicine Department of Internal Medicine, First Affiliated Hospital Sun Yat-sen University of Medical Sciences, Guangzhou, 510080,China)

    LI Chun-yi

    (Department of Nuclear Medicine Department of Internal Medicine, First Affiliated Hospital Sun Yat-sen University of Medical Sciences, Guangzhou, 510080,China)

    Abstract:Objective To evaluate the clinical significance of 99m Tc-MIBI and 201 T1 lung scintigraphy in the diagnosis of primary lung cancer. Methods Lung early(15~30 min) and delayed (3 h) planar scintigraphy were performed in 28 patients with lung cancer using 201 T1 and 23 patients simultaneously using 99m Tc-MIBI. Regions of interest were placed over the tumors (T) and contralateral normal lung tissue(N), and T/N ratio and retention index [RI=(dealyed T/N-early T/N)×100/early T/N]were calculated . Radioactivity uptake in tumor site above the normal lung tissue was considered as positive in optesthesia qualitative analysis. Results The positive rate was 86.96% in the early and 78.26% delayed images for 99m Tc-MIBI and 89.29% in both the early and delayed images for 201 T1. There was a significant difference (P<0.01) on the early T/N between 99m Tc-MIBI (1.26±0.19) and 201 T1 (1.43±0.21). The delayed T/N was 1.24±0.19 for 99m Tc-MIBI and 1.59±0.32 for 201 T1, and this difference was also significant (P<0.001). The delayed index was (-1.44±6.62)% for 99m Tc-MIBI and (10.83±11.80)% for 201 T1 (paired-samples t test, P<0.001). Conclusion 99m Tc-MIBI and 201 T1 lung scintigraphy have good positive prognostication in primary lung cancer diagnosis, but the retention index of 99m Tc-MIBI in the tumor areas are significantly lower compared with those of 201 T1. The results suggest 201 T1 is superior to 99m Tc-MIBI. The clinical value of 99m Tc-MIBI and 201 T1 scintigraphy in detecting lymph node metastasis in patients with lung cancer is to be further studied.
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    Key words:lung neoplasms/radionuclide imaging; lung neoplasms/diagnosis; technetium-99m-MIBI; Thallium-201▲

    201T1作为一种较好的亲肿瘤显像剂[1],在肺、脑以及甲状腺等肿瘤中的鉴别诊断价值已得到肯定。然而,由于其价格昂贵、且需加速器生产而使临床应用受限,因此,近年来对99m锝标记肿瘤阳性显像剂的研究已引起重视。99mTc-MIBI是目前最常用的心肌显像剂之一,其在肿瘤探测及良恶性鉴别诊断中的价值已有初步报道[2~6],本文对23例肺癌患者同时进行了201T1与99mTc-MIBI肺肿瘤显像,并进行了对比研究,现报告如下。

    1 资料与方法
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    1.1 临床资料

    28例病理组织证实的肺癌患者,男19例,女9例,平均年龄(58.46±14.31)岁(23~77岁)。其中鳞癌6例、腺癌11例、小细胞未分型癌2例、肺泡癌3例,未分型癌6例。所有患者均进行201T1肺显像,23例同时做99mTc-MIBI肺肿瘤阳性显像检查,两者相隔24 h,显像前均未进行放射等特殊治疗。

    1.2 显像方法

    1.2.1 99mTc-MIBI显像 患者平卧位,静脉注射740 MBq(20 mCi) 99m Tc-MIBI后,立即采集(2帧/s)胸部动态图像1 min,然后分别于30 min(早期相)及3 h(延迟相)进行胸部前后位、侧位平面显像,矩阵256×256,计数5×105
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    1.2.2 201T1显像 静脉给药剂量为111 MBq,注射后分别于15 min(早期相)及3 h(延迟相)进行多体位平面显像,设定能峰为(70±10)%,图像采集及处理同99mTc-MIBI显像。

    1.3 图像分析

    1.3.1 视觉分析 根据肺肿瘤部位放射性摄取程度将病变分为4级:摄取小于或等于正常肺组织为0级;摄取高于正常肺组织但明显低于心肌影像者为Ⅰ级,接近心肌影像为Ⅱ级,明显高于心肌影像为Ⅲ级。局灶性病变Ⅰ级以上、弥漫性病变Ⅱ级以上,提示肺肿瘤显像阳性。

    1.3.2 半定量分析 勾画各时相前位或后位图像上病变部位(T)及对侧正常肺组织(N)对应部位的镜影感兴趣区(ROI),计算ROI内总放射性计数、摄取比值(T/N)及滞留指数[RI=(延迟T/N-早期T/N)×100/早期T/N]。
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    1.4 仪器及药品

    东芝GCA-7200A/DI SPECT系统,配备低能平行孔通用准直器,显像剂99mTc-MIBI由中国原子能科学研究院广州医用同位素服务中心提供,201T1由上海科兴药业公司生产。

    1.5 统计分析

    计量资料以±s表示,采用配对t检验,计数资料的检验采用四格表确切概率法,显著水准0.05。

    2 结 果

    2.1 肺肿瘤显像在肺癌诊断中的阳性率

    取病灶部位放射性摄取较正常肺组织增高为阳性标准,本研究受检肺癌患者中99mTc-MIBI早期与延迟显像视觉性分析诊断肺癌的阳性率分别为86.96%(20/23)和78.26%(18/23),201T1显像两者阳性率均为89.29%(25/28),差异无显著意义(确切概率P>0.05)。结果还发现1例手术证实同时有腋下淋巴结及面部皮下结节转移的肺癌患者,99mTc-MIBI清晰显示了腋下转移病灶,而201T1显像无明显异常发现(图1)。
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    图1 右肺癌并腋下淋巴结转移肺显像

    Fig.1 Lung imaging of right lung cancer with metastataic focus in lymph node

    上排:201T1肺显像; 下排:99mTc-MIBI肺显像

    Upper row:201T1 imaging; Bottom row; 99m Tc-MIBI imaging

    2.2 99mTc-MIBI与201T1在肺癌组织中摄取的差异

    半定量分析结果,见表1。99mTc-MIBI早期与延迟显像摄取比值及滞留指数均低于201T1,两者差异有显著意义(t>7.30,P<0.001)。
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    表1 肺癌患者99mTc-MIBI和201T1肺显像摄取参数比较

    Table 1 Lung uptake information for 99m Tc-MIBI and 201 T1 in patients with lung cancer

    Early T/N

    Delayed T/N

    Retention index(%)

    99mTc-MIBI

    1.26±0.19

    1.24±0.19
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    -1.44±6.62

    201T1

    1.43±0.21

    1.59±0.32

    10.83±11.80

    t value

    5.538

    7.33

    4.307

    P

    <0.001

    <0.001
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    <0.001

    3 讨 论

    尽管目前用于肿瘤阳性显像的药物不少,但临床认可并获得广泛应用的主要为201T1与67Ga[1]。近年来,99mTc标记化合物在肿瘤显像中的研究逐渐增多,尤以99mTc-MIBI的临床应用引人注目[2~5],然而借助双核素显像同时探讨99mTc-MIBI与201T1应用价值的研究少见。Aktolum等[5]报道:在乳腺癌探测中,99mTc-MIBI的阳性率高于201T1,且在显像图上可见到更为明显的局灶性聚集。然而,我们在肺癌患者肿瘤阳性显像的研究中发现,201T1的阳性率较99mTc-MIBI稍高,尽管二者差异无显著意义,但延迟显像图上前者表现出更为持久的摄取,其结果与Hishiyama[4]及Yuksel等[6]的研究类似。导致我们与Aktolun所报道结果差异的原因之一是可能与肿瘤类型有关。
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    肿瘤阳性显像剂对良恶性肿瘤组织中摄取及滞留程度的差异是鉴别诊断的基础,优秀的显像剂应对恶性肿瘤具有高的摄取与滞留,而对良性病变中较低的摄取及较快的清除。我们对肺癌患者的研究结果表明:201T1早期与延迟肺显像所计算的T/N比值及滞留指数均较99mTc-MIBI明显增高(P<0.005),后者在延迟肺显像(3 h)中部分病例还呈现出缓慢的清除,滞留指数为(-1.44±6.62)%,国外也有报道达(-9.75±15.68)%[6]。二种显像剂在肺癌摄取与滞留的差异可能与其各自的细胞摄取机制有关。201T1在细胞的摄取依赖钠-钾ATP酶泵系统[7],受喹巴因(ouabain)的阻断[8],是一种主动、耗能的过程,恶性肿瘤摄取增高主要与细胞血流及代谢增加有关,因而在肺癌中表现为较高的摄取与滞留。与201T1不同,99mTc-MIBI借助其脂溶性和阳电荷性质通过被动扩散进入瘤细胞,其摄取主要依赖于病变细胞线粒体和细胞膜通透性增加[9],而瘤细胞血流与毛细血管渗透性改变仅起间接作用,随着血液示踪剂浓度的变化,瘤细胞呈现一定的清除,Matsui R等曾报道201T1在生长迅速的瘤细胞中较生长缓慢的瘤细胞显示出更慢的清除率,而MIBI在两者无明显区别[10]。尽管99mTc-MIBI在肺癌的评价中较201T1稍有逊色,但我们的结果初步表明99mTc-MIBI在肺癌淋巴结转移的诊断中具有一定的优势。最近的研究还发现[11]99mTc-MIBI可以与一种新的有机金属基质P糖蛋白(PGP)存在相互作用,后者可将化疗药物泵出细胞外而降低化疗效果,同时也可将99mTc-MIBI当作转运底物泵出,故肺癌若无明显99mTc-MIBI摄取,即提示化疗耐药可能,故可能用于预测肺癌化疗敏感性,对此,其它诸如CT、MRI及B超影像技术是难以做到的,然而有关这方面的工作有待深入研究。本文1例患者伴有淋巴结转移,99mTc-MIBI肺显像时在病变淋巴结具有较明显的聚集,但病例数太少,尽管显影的淋巴结可能给予有关转移灶的提示,但是否99mTc-MIBI较201T1更能发现病灶,尚难以做出肯定的结论。
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    我们及上述文献研究结果表明:99mTc-MIBI与201T1肺显像在原发性肺癌的诊断中均具有较高的阳性预测值,比较二者而言,201T1肺显像更具优越性,对于二者在肺癌淋巴结转移灶探测中的临床价值,有待更深入研究。■

    作者简介:梁宏(1963-),男,湖南连源人,副教授.

    参考文献:

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    [6]Yüksel M, Cermik T F, Yerlikaya N, et al. Is T1-201 supperior to Tc-99m-MIBI in the evaluation of primary lung cancer[J]. Eur J Nucl Med, 1998,25(8),1024(abstr).

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    [9]Chiu ML, Kronauge, J F, Piwnica-Worms D. Effect of mitochondrial and plasma membrane potentials on accumulation of Hexakis(2-methoxy isobutyl isonitrile) technetium(1) in cultured mouse ioroblasts[J]. J Nucl Med, 1990,31(10):1646.

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    [11]Piwnica W D, Chiu M L, Budding M, et al. Functional imaging of multidrug-resistant P-glycoprotein with an organotechnetium complex[J]. Cancer Res, 1993,53(5):977.

    收稿日期:1999-06-17, 百拇医药