99mTcN(NOEt)2与99mTc-MIBI在肿瘤模型显像中的对比研究

目的　探讨99mTc 氮 二 (N 乙基 N 乙氧基二硫代氨基甲酸盐 ) [99mTcN (NOEt) 2 ]应用于肿瘤诊断的可能性并与99mTc 甲氧基异丁基异腈(99mTc MIBI)肿瘤模型显像进行比较。方法　制备99mTcN (NOEt) 2 ,用上行薄层色谱法测定放化纯。各取 4只移植性艾氏腹水癌小鼠分别尾静脉注射99mTc MIBI或99mTcN(NOEt) 2 ,30min、2h、4h后进行全身后位静态显像。利用感兴趣区技术 ,分别计算不同时相肿瘤与头部 (T/H)、胸部 (T/C)、及健侧肢体对称部位 (T/L)的放射性比值。 4h后处死99mTcN (NOEt) 2 显像组小鼠 4只 ,取血并剥离脏器组织及肿瘤组织 ,称重 ,测量放射性计数 ,计算肿瘤与各脏器放射性比值。结果　99mTcN (NOEt) 2 室温下 4h保持稳定。99mTcN (NOEt) 2 选择性地有效的聚集于肿瘤组织。除腹部外其它组织靶 /非靶比值较高 ,注射2h后T/L比值达最高 ,为 4.87。99mTcN (NOEt) 2 显像组与99mTc MIBI显像组比较T/L比值差异有显著性 (P <0 .0 1)。体外测量肿瘤与血、肌肉、肺等脏器的单位重量放射性比值较高 ,与肝、小肠等腹部脏器的单位重量放射性比值较低。结论　在移植性艾氏腹水癌小鼠模型中99mTcN (NOEt) 2 从血液中清除很快 ,肿瘤摄取率高 ,有一定的滞留量 ,靶与非靶比值高 ,图像质量明显优于99mTc MIBI肿瘤     

食管癌^99mTc—HL91乏氧显像和HIF—1α表达水平的相关性研究

目的：研究食管癌^99mTc～HL91乏氧显像以及与乏氧诱导因子-1α（HIF—1α）表达水平的相关性。方法：50例食管癌患者行SPECT^99mTc—HL91乏氧显像,利用感兴趣区技术分别勾画各时相肿瘤（T）和相应正常食管部位（N）放射性计数比值,即T／N值,免疫组化方法检测肿瘤组织HIF-1α表达水平。结果：50例病灶对^99mTc—HL91的摄取均高于相应正常组织,^99mTc—HL91摄取程度与肿瘤病理分级无相关关系（P〉0．05）;注射^99mTc—HL914小时后SPECT显像颈段和胸上段食管癌T／N值为2．04±0．38,胸中段食管癌T／N值为2．16±0．32,胸下段食管癌T／N值为2．18±0．41,三者无显著性差异（P〉0．05）;病灶的T／N值为1．36—4．43（中位值2．45）,免疫组化结果显示表达HIF—1α的细胞数为23．1％-76．9％（中位数52．9％）,两者之间呈正相关（P〈0．05）。结论：食管癌组织对乏氧显像剂^99mTc—HL91有显著摄取,摄取值与肿瘤病理分级及病变部位无相关性,但与HIF-1α的表达正相关。     

卵巢癌多药耐药^99mTc—MIBI显像的研究现状及临床应用进展

卵巢癌多药耐药（MDR）是导致化疗失败的一个重要原因,无创性诊断卵巢癌多药耐药一直是临床研究热点。其作用机制主要与P糖蛋白（P-gp）、MRP相关蛋白（MRP）及肺耐药蛋白（LRP）等有关。甲氧基异丁基异腈（MIBI）是P—gp、MRP共同的转运底物,细胞内^99mTc—MIBI的摄取浓度与细胞上MDR表达的功能状态成反比。因此利用^99mTc—MIBI功能显像对卵巢癌定性诊断、评价多药耐药及预测化疗效果,指导临床选择个体化的治疗方案可能有很高的临床应用价值。     

原发性肺癌99mTc-MIBI显像与多药耐药蛋白表达的关系

目的：探讨原发性肺癌对^99mTc-MIBI摄取和滞留与三种多药耐药蛋白表达的关系及临床意义。方法：对26例原发性肺癌患者静脉注射925MBq^99mTc—MIBI后15min和120min分别行SPECT显像．采用感性趣区（ROI）技术计算早期和延迟相肿瘤／非肿瘤（T／N）比值以及滞留率RI％。采用免疫组化法检测肺癌组织多药耐药蛋白P—gp、MRP和GSTπ表达水平，并与T／N和RI％进行相关性分析：结果：^99mTc—MIBI显像阳性率为92．31％；P—gp、MRP、GST耵表达阳性率分别为75．00％、58．33％、45.83％，三者无明显差别（X^2=4．273，P=0．118）。P-gp＋MRP、P—gp＋GSTπ、MRP＋GSTπ、p-gp＋MRP＋GSTπ其表达阳性率分别为41.67％、37．50％、29.17％、20．83％；P—gp表达阳性组和阴性组RI％间有显著性差异（t=-2.258，P=0．034）．结论：^99mTc—MIBI显像能预测肺癌组织P—gp的表达水平，为临床个体化治疗提供理论依据。     

肺癌多药耐药的^99mTc-MIBI显像

肺癌多药耐药(MDR)是导致化疗失败的一个重要原因，其作用机制主要与P-糖蛋白(P-gp)和MDR相关蛋白(MRP)有关。甲氧基异丁基异腈(MIBI)是P-gp、MRP共同的转运底物，细胞内^99mTc-MIBI的摄取浓度与细胞上MDR表达的功能状态成反比。利用^99mTc-MIBI功能显像能无创性地评估MDR，预测肿瘤对化疗的反应性，指导临床选择更加个体化的治疗方案。     

99m Tc-MIBI及67 Ga肺显像诊断原发性肺癌的对比研究

目的 :评价 99mTc MIBI (锝—甲氧基异丁基异腈 )及 67Ga (镓 )肺肿瘤显像诊断原发性肺癌的临床价值。方法 :对 72例肺癌患者均进行了 99mTc MIBI与 67Ga肺肿瘤显像 ,勾画病变部位 (T)及对侧正常肺组织 (N)对应部位的感兴趣区 (ROI) ,计算摄取比值 (T/N)及滞留指数RI =(延迟T/N—早期T/N)× 10 0 /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 :99mTc MIBI及 67Ga诊断肺癌的阳性率分别为 72 .2 %、91.7% ,两者结合阳性率为 97 2 %。99mTc MIBI及 67Ga显像对纵隔淋巴结转移的阳性率分别为 85 .7%、5 0 .0 %。结论 :99mTc MIBI及 67Ga两者联合应用可提高肺癌的阳性检出率。单独使用时 ,67Ga显像在显示肺癌部位上具有优越性 ,在显示纵隔淋巴结转移灶中99mTc MIBI占优势。     

分化型甲状腺癌术后^99Tc^m—MIBI显像与^131 I显像比较及其意义

目的：探讨分化型甲状腺癌（DTC）术后^99Tc^m—MIBI显像结果的意义。方法：300例DTC术后患者中随机选取69例行^99Tc^m-MIBI显像。2名有经验核医学医师盲法阅片。将^99Tc^mMIBI显像结果与治疗后^131I显像结果比较。另对经高分辨CT或治疗后^131 I显像诊断肺转移和无肺转移患者行半定量分析,比较靶本底比值（T／B）。结果：排除1例死于血管肉瘤者,余按照手术方式及^131 I治疗情况分为3组（A组：44例甲状腺癌术后拟^131I治疗组;B组：22例有再次^131I治疗指征组;C组：2例甲状腺大部切除组）。A组^99 Tc^m-MIBI显示残余甲状腺34．1％（15／44）,转移灶30．0％（6／20）。B组^9^Tc ^m-MIBI显示复发及转移灶63．6％（7/11）。C组^99Tc^mMI—BI显示残余甲状腺100．0％（2／2）,并为唯一一种发现颈部转移显像方法。5例患者同时存在多种性质转移灶：MI—BI＋I-,MIBI-I＋及MIBI＋I＋。肺转移与无肺转移患者T/B比值差异无统计学意义。结论：^99Tc^m -MIBI可发现分化好及失分化病灶,联合^131 I显像为DTC术后患者选择治疗方式提供重要信息,有临床应用价值。     

^99mTc-MIBI脑显像预测高分级脑胶质瘤同步放化疗疗效的临床研究

目的探讨99m锝-甲氧基异丁基异晴（technetium-99m methoxyisobutylisonitrile,^99mTc-MIBI）脑显像预测高分级脑胶质瘤同步放化疗疗效的可能性。方法用SPECT／CT对67例高分级脑胶质瘤进行脑显像,于放化疗前肘静脉注射^99mTc-MIBI30mCi,注射后30分钟和120分钟分别行早期相和延期相显像,计算肿瘤感兴趣区（region of interest,ROI）与对侧正常相应部位早期摄取比值（T／Ne）、延期摄取比值（T／Nd）和滞留率（RI％）。所有患者给予术后病灶三维适形放疗和替莫唑胺（temozolomide,TMZ）同步化疗,随后给予6个周期的TMZ辅助化疗。结果放化疗有效组49例（71．1％）,中位生存期（MST）19月;无效组18例（28．9％）,MST11月,两者MST比较差异有统计学意义（P〈0．05）,前者T／Ne、T／Nd和RI％值为4．65±2．17、6．67±3．32及（16．11±2．35）％;后者为6．14±2．06、4．47±2．57及（5．40±2．61）％,T／Ne和T／Nd值比较差异无统计学意义（P〉0．05）,RI％值比较差异有统计学意义（P〈0．05）。结论99mTc-MIBI脑显像中RI％对高分级脑胶质瘤同步放化疗疗效有一定的预测作用。     

^99mTc-MIBI全身显像在^131Ⅰ治疗分化型甲状腺癌转移灶中的应用价值

目的^99 mTc-MIBI全身显像对^131Ⅰ治疗分化型甲状腺癌转移灶或复发灶的疗效评价及预后评估。方法患者依次行Tg测定、^99 mTc-MIBI全身显像和^131Ⅰ全身显像,三项结果进行对比,并结合其它必要检查及病理分析。结果^99 mTc-MIBI全身显像阳性的患者表现为转移灶摄取^99 mTc-MIBI的量与摄取^131Ⅰ的量成反比,^131Ⅰ疗效差的转移灶摄取^131Ⅰ量较少,而摄取^99 mTc-MIBI量较多,^131Ⅰ疗效较好的转移灶摄取^131Ⅰ量较多,而摄取^99 mTc-MIBI量较少;Tg水平超过正常值的患者,均发现有转移灶。结论^99 mTc-MIBI显像可观察转移灶变化并相对推测转移灶的细胞分化程度及^131Ⅰ的疗效;联合三种检查可提高转移灶检出率,减少漏诊。     

^99mTc—MIBI显像在乳腺癌诊断中的应用

目的：寻找有效和无创性诊断乳腺癌及腋窝淋巴结转移的方法。方法：对36例乳腺肿瘤患者进行了乳腺及其区域淋巴结^99mTc-MIBI显像。全部肿瘤经病理证实。结果：36例乳腺肿瘤中14例为良性肿瘤，22例为乳腺癌，其中腋窝淋巴结转移者13例。^99mTc-MIBI显像诊断乳腺肿瘤假阳性1例，假阴性4例，其灵敏度为81．8％，特异性为92．6％，准确性为86．1％；^99mTc-MIBI显像诊断乳腺癌腋窝淋巴结转移假阴性5例，未发现假阳性，其灵敏度为100％，特异性为61．5％，准确性为77．3％。结论：^99mTc-MIBI显像诊断乳腺恶性肿瘤灵敏度较高，是一种有效的无创性诊断方法，也有助于诊断乳腺癌腋窝淋巴结转移，但是其结果还不够理想，有待于进一步研究。     

鼻咽癌99m↑Tc-HL91乏氧显像与HIF-1α的相关性研究

目的研究鼻咽癌99m↑Tc-HL91乏氧显像特征及其与HIF-1α表达的相关性。方法对12例鼻咽癌初诊患者静脉注射99m↑Tc-HL91 740-1110 MBq（20～30 mCi）1 h及4 h后,分别行平面及SPECT断层扫描,应用计算机感兴趣区（ROI）,分别勾画各时相的鼻咽肿瘤和颈部淋巴结（T）与对侧相应部位（N）的感兴趣区,计算两者的比值得到T/N值。采用免疫组化法检测肿瘤组织HIF-1α表达水平。结果 12例患者鼻咽部位和（或）颈部淋巴结转移灶均见示踪剂浓集。注射99m↑Tc-HL91示踪剂4 h后病灶显影较1 h明显（P〈0.01）。99m↑Tc-HL91断层图像T/N比值始终高于平面图像（P〈0.01）,而且图像更清晰。示踪剂在鼻咽癌肿瘤部位的浓集与在颈部淋巴结转移灶的浓集无统计学差异（P〉0.05）。HIF-1α阳性表达细胞占总细胞数的百分率为39.8%～77.8%（中位数56.4%）。HIF-1α表达与HL91断层图像上鼻咽肿瘤病灶对示踪剂的摄取明显相关（P〈0.05）,而与颈部淋巴结转移灶对HL91的摄取及平面图像上鼻咽肿瘤病灶的摄取无关（P〉0.05）。结论鼻咽癌原发肿瘤病灶和（或）颈部转移淋巴结对乏氧显像剂99m↑Tc-HL91摄取显著,4h后病灶显影较1 h明显。99m↑Tc-HL91断层图像上鼻咽肿瘤病灶对示踪剂的摄取与HIF-1α的表达呈正相关。     

Scintimammographic findings of phyllodes tumor of the breast in a double-phase study with Tc-99m (V)DMSA and Tc-99m MIBI: a case report

We present a case of phyllodes tumor of the breast in a 78-year-old woman evaluated with Tc-99m (V)DMSA and Tc-99m MIBI scintimammography, acquired in separate sessions (10 and 60 min post-injection). Tc-99m (V)DMSA was accumulated intensely within the mass [tumor to background ratio (T/B) >3], whereas Tc-99m MIBI had significantly lower uptake (T/B 1.9). Histology revealed a phyllodes tumor (maximum diameter 15 cm) and approximately three mitoses over 10 fields of view (FOV) x40, foci of epithelial hyperplasia and apocrine metaplasia. Stromal Ki-67 expression was 7%. The tumor was considered to be benign and the patient underwent mastectomy. One year later the patient presented with local malignant recurrence of the disease with over 15 mitoses per 10 FOV. Tc-99m (V)DMSA seems to have an advantage over Tc-99m MIBI in detecting mesenchymal tumors with unforeseen biological behavior and Ki-67 over-expression, such as phyllodes tumors, even with primary negative histological findings.     

Hypoxia imaging predicts success of hypoxia-induced cytosine deaminase/5-fluorocytosine gene therapy in a murine lung tumor model

Tc-99m-HL91 is a hypoxia imaging biomarker. The aim of this study was to investigate the value of Tc-99m-HL91 imaging for hypoxia-induced cytosine deaminase (CD)/5-fluorocytosine (5-FC) gene therapy in a murine lung tumor model. C57BL/6 mice were implanted with Lewis lung carcinoma cells transduced with the hypoxia-inducible promoter-driven CD gene (LL2/CD) or luciferase gene (LL2/Luc) serving as the control. When tumor volumes reached 100?mm(3), pretreatment images were acquired after injection of Tc-99m-HL91. The mice were divided into low and high hypoxic groups based on the tumor-to-non-tumor ratio of Tc-99m-HL91. They were injected daily with 5-FC (500?mg?kg(-1)) or the vehicle for 1 week. When tumor volumes reached 1000?mm(3), autoradiography and histological examinations were performed. Treatment with 5-FC delayed tumor growth and enhanced the survival of mice bearing high hypoxic LL2/CD tumors. The therapeutic effect of hypoxia-induced CD/5-FC gene therapy was more pronounced in high hypoxic tumors than in low hypoxic tumors. This study provides the first evidence that Tc-99m-HL91 can serve as an imaging biomarker for predicting the treatment responses of hypoxia-regulated CD/5-FC gene therapy in animal tumor models. Our results suggest that hypoxia imaging using Tc-99m-HL91 has the predictive value for the success of hypoxia-directed treatment regimens.     

The role of technetium‐99m methoxyisobutyl isonitrile scintigraphy in predicting the therapeutic effect of chemotherapy against nasopharyngeal carcinoma

BACKGROUND:

The authors prospectively evaluated the correlation between technetium‐99m methoxyisobutyl isonitrile (^99mTc‐MIBI) accumulation in tumors and response to induction chemotherapy in patients with nasopharyngeal carcinoma (NPC).

METHODS:

Eighty‐six patients with locally advanced NPC underwent single‐photon emission computed tomography 15 minutes after an intravenous injection of 740 megabecquerels (20 mCi) ^99mTc‐MIBI before chemotherapy. The tumor uptake ratio (TUR) was calculated. Two weeks after the second cycle of combined chemotherapy with 5‐fluorouracil (5‐FU) and cisplatin (DDP), the tumor response rate was evaluated. The correlation between ^99mTc‐MIBI accumulation in tumors and response to chemotherapy with 5‐FU/DDP was examined.

RESULTS:

Positive accumulation of ^99mTc‐MIBI in tumors was observed in 76 patients (88.4%). The tumor response was a complete response (CR) in 8 patients, a partial response (PR) in 68 patients, stable disease (SD) in 9 patients, and progressive disease (PD) in 1 patient. The response rate (CR and PR) to 5‐FU/DDP chemotherapy in patients who had positive ^99mTc‐MIBI accumulation (tumor uptake ratio [TUR] >1.1) was higher than that in patients who had negative ^99mTc‐MIBI accumulation (TUR ≤1.1; 98.7% vs 10%; P < .001).

CONCLUSIONS:

Patients with negative ^99mTc‐MIBI accumulation were resistant to 5‐FU/DDP chemotherapy. ^99mTc‐MIBI imaging in patients with NPC was capable of predicting tumor response to chemotherapy with 5‐FU/DDP and can help in the selection of patients for induction chemotherapy. Cancer 2011. © 2010 American Cancer Society.     

99mTc-MIBI肺肿瘤显像与MRP表达的关系

目的:探讨原发性肺癌99mTc-MIBI显像与多药耐药相关蛋白(MRP)表达的关系。方法:对22例原发性肺癌行99mTc-MIBI早期(30min)、延迟(180min)显像,应用免疫组化方法检测手术标本中MRP表达水平,比较早期摄取比值(EUR)、晚期摄取比值(DUR)及储留指数(RI)与MRP表达的关系。结果:99mTc-MIBI早期、延迟显像阳性率分别为90.9%、81.8%,MRP表达阳性率27.3%;MRP表达阳性组与阴性组间与99mTc-MIBI的EUR、DUR及RI未见显著性差异。结论:原发性肺癌组织对99mTc-MIBI聚集、洗脱与MRP表达关系不大,应用99mTc-MIBI显像检测原发性肺癌MRP基因的表达临床价值不大。     

^99Tc^m-MIBI SPECT预测小细胞肺癌CE方案化疗疗效的临床研究

目的：探讨^99Tc^m-MIBI摄取与小细胞肺癌（SCLC）CE方案化疗疗效的关系。方法：48例SCLC患者根据胸部CT分为化疗有效组（完全缓解＋部分缓解）和无效组（进展加重＋无缓解），于化疗前行^99Tc^m-MIBI肺显像，静脉注射^99Tc^m-MIBI 740MBq后10～30min及2～3h分别行早期及延迟显像，在^99Tc^m-MIBI显像的断层图上用感兴趣区（ROI）的方法，勾画出病灶，然后镜像ROI于健侧肺的相应部位，由此分别获得早期相肿瘤／正常肺组织摄取比值（ER）和延迟相肿瘤／正常肺摄取比值（DR），并计算出滞留指数（RI％）=100×（DR—ER）／ER。分析化疗有效组与化疗无效组ER、DR和RI之间的差别。结果：^99Tc^m-MIBI显像结果中，化疗有效组和无效组平均ER、DR和RI比较差异有统计学意义（t=2．5738，P〈0．02；t=4．8291，P〈0．001；t=4．7331，P〈0．001），化疗有效组的ER、DR、RI均高于无效组。结论：^99Tc^m-MIBI显像的ER、DR和RI可能有助于预测SCLC患者CE方案化疗的疗效。     

Technetium-99m methoxyisobutylisonitrile chest imaging for small-cell lung cancer

Aims:This is a retrospective and adaptive randomizationstudy. The purpose of this study was to evaluate the relationshipbetween technetium-99m methoxyisobutylisonitrile (Tc-99m MIBI)chest-imaging results, chemotherapy response and P-glycoprotein (Pgp) ormultidrug resistance related protein (MRP) expression in small-cell lungcancer (SCLC). Patients and methods:Beforechemotherapy, 30 patients (11 females, 19 males, ages: 52–69years) with SCLC, including 14 extensive diseases without localizedproblems and 16 limited diseases in excess of solitary pulmonary nodule,underwent early chest imaging, including visual interpretation andquantitative analyses of tumor uptake ratio (TUR), 10 minutes afterintravenous injection of Tc-99m MIBI. Immunohistochemical analyses wereperformed, using multiple nonconsecutive sections of the biopsyspecimens, to detect Pgp and MRP expressions. Chemotherapy response wasevaluated in the third month after completion of treatment by clinicaland radiological methods. Results:All 15 (100%)of the SCLC patients with complete or partial response had positiveTc-99m MIBI chest SPECT results, but negative ones for both Pgp and MRPexpression. Twelve of the 15 (80%) SCLC patients with no responseor progressive disease had negative Tc-99m MIBI chest SPECT results andwere positive for either Pgp or MRP expression(P < 0.05). Negative Tc-99m MIBI chest SPECTresults predicted complete or partial response. The TUR of patients withcomplete or partial response (1.91 ± 0.29 with a 95%confidence interval (95% CI): 1.75–2.07) was significantlyhigher than that of patients with no response or progressive disease(1.19 ± 0.28 with a 95% CI: 1.04–1.35). Conclusion:Tc-99m MIBI chest images are a potential toolfor understanding Pgp and MRP expressions in SCLC and for predictingpatient chemotherapy response.     

新型肿瘤新生血管靶向分子探针99mTc-RRL的合成及初步研究

[目的]探讨新型肿瘤新生血管显像剂99mTc-RRL的合成与标记及其在不同肿瘤动物模型中的初步显像效果,评价99mTc-RRL用于肝癌裸鼠模型体内的生物分布特点。[方法]固相合成法合成RRL,与99mTc进行标记。制备不同类型肿瘤动物模型,并进行单光子计算机断层（SPECT）显像。荷瘤HepG2肝癌裸鼠尾静脉注射99mTc-RRL后,于不同时刻处死动物,取感兴趣器官和组织称重并测量其放射性计数,计算各器官或组织的%ID/g值。同时,高锝酸钠阴性对照组、非标记RRL竞争阻断组采用同样方法,计算其6h时刻各脏器或组织的%ID/g值。HE染色和CD34免疫组化方法用于评价瘤体新生血管状态及分子探针检测阈值的相关性分析。[结果]99mTc-RRL标记率达80%,放射化学纯度高,体外稳定性好。SPECT显像示肿瘤部位见显影,轮廓清晰,放射性明显高于其他器官,随时间延长,肿瘤部位有持续放射性聚集。生物分布数据显示99mTc-RRL血液清除快,肿瘤部位显示放射性持续滞留,提供良好靶/非靶组织比值。HE染色和免疫组化结果显示了瘤体旺盛的血管生成;瘤体大小与探针摄取量呈明显正相关关系。[结论]99mTc-RRL能够特异性地聚集于不同类型肿瘤组织。体内生物分布好,可提供良好的靶/非靶组织比值,是具有应用价值的肿瘤新生血管靶向示踪剂。