~(99m)Tc-octre otide和~(111)In-DTPA-octre otide受体显像诊断肿瘤的比较研究

[目的]对比研究 99mTc octreotide和 111In DTPA octreotide受体显像对肿瘤诊断的效能。[方法]采用自行制备的111In_DTPA_octreotide和99mTc octreotide分别对4例和3例正常对照以及对18例和12例肿瘤患者进行显像 ,以发现局灶性异常放射性浓集为阳性 ,比较其对肿瘤诊断的效能。[结果]两种显像剂的正常图像、显像质量和对生长抑素受体(SMS R)阳性肿瘤的诊断效能无显著差异 ,两种显像剂显像结果均与临床最后诊断相符合。[结论]99mTc octreotide是一种价廉易得的优良的肿瘤SMS R显像剂 ,在临床上可以替代价格高昂不易获得的111In DTPA octreotide进行肿瘤显像     

99mTc—octreotide体外受体结合方法及特性研究

目的：探讨99m Tc-octreotide(奥曲肽，一种人工合成的生长抑制8肽类似物）体外受体结合方法及其结合特性，为生长抑素肿受体显像提供实验依据。方法：以最大结合率为标准，分别改变细胞膜受体结合反应体系的温度，温育时间，细胞膜量和标记肽量等因素。建立99m-Tc-octreotide体外受体结合方法，并在此基础上进行饱和实验和竞争抑制实验，和以99m Tc-oxytocin(催产素）作为对照物进行比较实验，结果：Wistar大鼠脑皮质细胞体外放射受体分析最大结合率36．9％，非特异性结合10．3％，饱和实验，竞争抑制实验和对照实验结果：99mTc-octreotide具有可饱和及竞争抑制的受体结合特性，K0=0.82nM,Bmax=7.86nM.结论：octreotide经99m Tc标记后，仍具有受体结合活性。有希望作为具有临床衫价值的生长抑制肿瘤受体显像剂。     

人小细胞肺癌NCI-H446裸鼠模型的99mTc-octreotide受体显像研究

背景与目的小细胞肺癌恶性程度高,早期诊断对其预后有重要价值,目前的检查方法比较局限,传统影像学方法特异性差,而PET/CT价格昂贵,难于推广应用。小细胞肺癌属神经内分泌肿瘤,高表达生长抑素受体,是其早期进行分子影像诊断的理论基石。本实验旨在观察99mTc-octreotide在正常裸鼠体内的分布、代谢及荷人NCI-H446小细胞肺癌裸鼠模型体内显像变化,为临床小细胞肺癌早期诊断奠定基础。方法建立人小细胞肺癌的裸鼠肿瘤模型,正常裸鼠及荷瘤鼠静脉注射99mTc-octreotide显像剂后行动态及延迟显像。运用感兴趣区（regionofin-terest,ROI）技术勾画各时相裸鼠各脏器、肿瘤（T）及肿瘤对侧对应部位（N）放射性计数,计算相应T/N比值,并建立30min内各ROI的时间-放射性（A-T）曲线。结果①正常裸鼠的肾脏、肝脏内99mTc-octreotide分布最多,肺部、心脏部位分布较低,头部放射性分布最少,99mTc-octreotide主要通过泌尿系统排泄;各脏器30min内A-T曲线显示放射性分布随时间延迟呈逐渐下降趋势。②5例荷瘤裸鼠的肿瘤显像均呈阳性;静脉注射99mTc-octreotide后肿瘤部位在3h显像最清楚,整个检查时间内肝脏放射性强度明显高于肿瘤组织,肺部放射性与肿瘤部位较相近。半定量分析结果显示,静脉注射99mTc-octreotide后肿瘤组织与对侧肢体肌肉的T/N比值在0.5h、2h、3h、4h分别为1.163±0.03、2.08±0.12、3.03±0.23、2.689±0.31;各时相T/N比值差异有统计学意义（F=51.69,P<0.000,1）;通过两两比较发现,静脉注射显像剂后3h的T/N比值与其他各时相差异均有统计学意义（P<0.05）;不同检查时间肝脏部位的放射性平均计数高于肿瘤部位,肺部的平均计数与肿瘤相近。肿瘤部位A-T曲线显示,注射99mTc-octreotide后2min-3min出现一过性放射性分布高峰。结论运用99mTc-octreotide作显像剂,人小细胞肺癌NCI-H446裸鼠模型具有极高的显像阳性率,且3h肿瘤显像最清楚。     

^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。     

肺癌核素肿瘤显像假阴性时结合骨显像的临床意义

目的：探讨肺癌患者核素^99Tc^mMIBI肿瘤显像出现假阴性和可疑阳性结果时联合应用^99Tc^m-MDP全身骨显像的价值及临床意义。方法：肺癌患者42例，均同时行^99Tc^m-MIBI肺肿瘤显像与^99Tc^m-MDP全身骨显像，将两种显像结果进行对照，分析两种方法联合应用对肺癌的诊断价值。结果：42例肺癌患者中，^99Tc^m-MIBI肺肿瘤显像阳性18例，阴性10例，可疑阳性14例，阳性率76．2％。骨显像示，肺癌骨转移者24例，骨转移发生率57．14％。两种方法联合应用诊断肺癌的阳性率为90．48％。结论：肺肿瘤显像与全身骨显像联合应用可提高肺癌诊断的阳性率，并有助于肺癌的临床分期与治疗方案的制订，值得临床推广。     

^99Tc^m奥曲肽核素显像诊断结直肠癌的研究

目的：探讨^99Tc^m奥曲肽显像对结直肠癌的诊断价值。方法：30例经内窥镜检查活检病理确诊的结直肠癌及6例非结直肠癌患者,术前进行腹部的^99Tc^m奥曲肽显像,以^99Tc^m直接标记的奥曲肽进行分析。结果：^99Tc^m奥曲肽显像检测30例结直肠癌4例阳性,26例阴性;6例非结直肠癌2例阳性,4例阴性。^99Tc^m奥曲肽显像对结直肠癌诊断的敏感度、特异度和准确度分别为13.33%、33.33%和22.22%。结论：^99Tc^m奥曲肽显像是一种无创、安全、经济的检查方法,但对结直肠癌诊断价值有限;需要用各种亚型的生长抑素受体和扩大样本量做进一步研究,以提高诊断的准确度。     

核素标记血管多肽显像诊断恶性肿瘤实验研究

[目的]以肿瘤血管系统为目的靶，以核素标记多肽ATWLPPR为显像剂，探讨核素标记肿瘤血管特异性多肽显像用于肿瘤诊断的可行性。[方法]应用^99mTc标记ATWLPPR并鉴定。制作荷人乳腺癌裸鼠模型，实验组于注射^99mTc-ATWLPPR后不同时间显像，对照组应用未标记ATWLPPR预处理后显像，勾画感兴趣区，计算两组肿瘤与对侧相应部位放射性比值。荷瘤裸鼠于注射显像剂后180min，取感兴趣器官及肿瘤组织称重并测量放射性计数。[结果]以HYNIC作为双功能螯合剂，^99mTc-HYNIC—ATWLPPR标记率可达91．53％±2．39％，放化纯为94．14％±1．75％，标志物体外稳定。实验组荷瘤裸鼠注射显像剂后180min肿瘤部位显影最为清晰，对照组肿瘤部位未见明显显像剂分布，两组肿瘤／对侧上肢的放射性比值分别为2．33±0．40和1．18±0．12（P〈0．05）。显像剂在荷乳腺癌裸鼠体内肝脏和肾脏的摄取最高，脑部摄取最低。[结论]制备的^99Tc-HYNIC-ATWLPPR方法简单，标记率和放化纯高、稳定性好，主要以肝脏和肾脏排泄，肿瘤组织可以对该品像剂特异忡格取辊示该显像剂可以用于肿瘤诊断．     

^18F—FDGPET显像与^99Tc^m-MDP全身骨显像诊断肿瘤骨转移价值的比较

目的评价^18F-脱氧葡萄糖（FDG）PET肿瘤显像与^99Tc^m-亚甲基二膦酸盐（MDP）全身骨显像诊断肿瘤骨转移价值。方法43例肿瘤患者,其中28例经其他检查或随访证实为骨转移,15例证实无骨转移。2周对患者内行^18F—FDGPET和^99Tc^m-MDP显像,比较分析两种显像结果。结果28例肿瘤骨转移患者中,^18F—FDG PET阳性26例,^99Tc^m-MDP阳性27例,灵敏度分别为92．9％（26／28）、96.4％（27／28）,差异无统计学意义（P〉0．05）。15例无骨转移患者中,PET阴性14例,MDP阴性8例,特异度分别为93．3％（14／15）、53．3％（8／15）,差异有统计学意义（P〈0．01）。两种方法检测骨转移的准确率分别为93．0％（40／43）、81．4％（35／43）,差异有统计学意义（P〈0．01）。结论^18F—FDGPET诊断肿瘤骨转移的灵敏度与^99Tc^m-MDP显像相近,但特异性和准确性均较高。对^99Tc^m-MDP骨显像阴性、单一病灶及可疑骨转移患者,进一步行^18F—FDG PET显像,可起到信息互补、明确诊断的作用。     

^99mTc（V）—DMSAD在肿瘤诊断中的作用

五价锝标记的二巯基丁二酸（^99mTc(V)-DMSA)是近年来研究较多的肿瘤阳性显像剂，其在甲状腺髓样癌、软组织胛瘤、头颈部肿瘤、骨转移瘤等多种恶性肿瘤的显像诊断中显示了较高的灵敏度和特异性，在恶性肿瘤诊断中有着广泛的应用前景。现对699mTc(V)－DMSA在肿瘤显像诊断中的应用予以综述。     

^99Tc^m—MIBI显像在乳腺肿瘤中的临床分析

目的：评价^99Tc^m-MIBI乳腺显像对乳腺肿瘤和腋窝淋巴结转移的诊断价值。方法：52例女性乳腺肿瘤患者，体检腋窝未扪及肿块。应用^99Tc^m-MIBI740MBq(20mCi)经肘静脉注射，行乳腺和腋窝显像，并用手术、病理加以对照。结果：48例乳腺肿瘤患者中，^99Tc^m-MIBI显像真阳性32例，灵敏度为84％(32／38例)，特异性60％(6／10例)，准确性79%，40例乳腺癌腋窝淋巴结的灵敏度为71％(10／14例)，特异性88％(23／26例)，准确性83％。结论：^99Tc^m-MIBI乳腺显像既可以显示乳腺肿瘤又能了解腋窝淋巴结的灵敏度为71％(10／14例)，特异性88％(23／26例)，准确性83％。结论：^99Tc^m-MIBI乳腺显像既可以显示乳腺肿瘤又能了解腋窝淋巴结，是核素乳腺显像的首选方法之一。     

Long-term octreotide treatment of metastatic carcinoid tumor

The optimal dosage of somatostatin analogs for the long-term control ofcarcinoid tumors has not yet been established. Receptor alterations inducedduring long term treatment with somatostatin analogs have lead to consecutivedrug dosage increases in order to control carcinoid disease. In this report,we describe the rapid and effective control of tumor in a patient withmetastatic carcinoid treated for nine years with a single daily dose ofoctreotide based on tumor marker levels. Tumoral somatostatin receptor (sst)subtype analysis by RT-PCR amplification showed the expression ofsst₂ subtype only. We suggest that a single daily dose ofoctreotide strictly related to tumor marker secretion, could have played arole in the effective long-term therapy by avoiding the phenomenon ofsomatostatin receptor desensitisation. Furthermore, the exclusive presence ofsst₂ subtype supports the high affinity of octreotide to tumoralcells.     

Pneumonia can cause 111Indium octreotide uptake

An 18‐year‐old woman underwent an ¹¹¹In octreotide scan for evaluation of a possible insulinoma. This showed mildly increased radiopharmaceutical uptake involving the right lung base. The patient reported a productive cough for 5 days before the octreotide scan. A chest radiograph was taken, which showed increased airspace opacification in the right lower lobe, corresponding to the uptake seen on the octreotide scan. After a course of oral antibiotics, the patient’s chest symptoms improved and the radiograph opacification resolved, confirming the diagnosis of community‐acquired pneumonia. This case stresses the need to correlate scan results with the patient’s presentation and symptoms to avoid false‐positive data.     

Optimized labeling of NOTA-conjugated octreotide with F-18

We recently reported a facile method based on the chelation of [¹⁸F]aluminum fluoride (Al¹⁸F) by NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid). Here, we present a further optimization of the ¹⁸F labeling of NOTA-octreotide (IMP466). Octreotide was conjugated with the NOTA chelate and was labeled with ¹⁸F in a two-step, one-pot method. The labeling procedure was optimized with regard to the labeling buffer, ionic strength, peptide concentration, and temperature. Radiochemical yield, specific activity, in vitro stability, and receptor affinity were determined. Biodistribution of ¹⁸F-IMP466 was studied in AR42J tumor-bearing mice. In addition, microPET/CT images were acquired. IMP466 was labeled with Al¹⁸F in a single step with 97% yield in the presence of 80% (v/v) acetonitrile or ethanol. The labeled product was purified by HPLC to remove unlabeled peptide and unbound Al¹⁸F. The radiolabeling, including purification, was performed for 45 min. Specific activities of 48,000 GBq/mmol could be obtained. ¹⁸F-IMP466 showed a high tumor uptake and excellent tumor-to-blood ratios at 2 h post-injection. In addition, the low bone uptake indicated that the Al¹⁸F–NOTA complex was stable in vivo. PET/CT scans revealed excellent tumor delineation and specific accumulation in the tumor. Uptake in receptor-negative organs was low. NOTA-octreotide could be labeled with ¹⁸F in quantitative yields using a rapid two-step, one-pot, method. The compound was stable in vivo and showed rapid accretion in SSTR₂-receptor-expressing AR42J tumors in nude mice. This method can be used to label other NOTA-conjugated compounds such as RGD peptides, GRPR-binding peptides, and Affibody molecules with ¹⁸F.     

奥曲肽治疗晚期原发性肝癌的疗效观察

目的:观察生长抑素类似物奥曲肽治疗晚期原发性肝癌的临床疗效.方法:收集40例晚期原发性肝癌患者,治疗组20例,使用奥曲肽0.2mg,皮下注射,每12小时1次,直至病情进展停药;对照组20例,仅接受积极的支持治疗,每1个月进行1次疗效评价,比较两组疗效.结果:治疗组中无CR,1例PR,4例MR,6例SD,9例PD.总有效率为25%;对照组中无CR、PR、MR,6例SD,14例PD,总有效率为O%,两组有显著性差异(P<0.05).治疗组中位生存期为6.5个月,对照组中位生存期为2.5个月(P<0.05);治疗组TTP为3.5个月,对照组1.5个月(P<0.05);治疗组较对照组患者的AFP水平明显下降(P<0.05),生活质量有明显提高,上消化道出血的发生率降低(P<0.05).结论:奥曲肽治疗晚期原发性肝癌能有效延长患者的生存期,提高生活质量.     

奥曲肽治疗晚期原发性肝癌的疗效观察

目的：观察生长抑素类似物奥曲肽治疗晚期原发性肝癌的临床疗效。方法：收集40例晚期原发性肝癌患者,治疗组20例,使用奥曲肽0.2mg,皮下注射,每12小时1次,直至病情进展停药;对照组20例,仅接受积极的支持治疗,每1个月进行1次疗效评价,比较两组疗效。结果：治疗组中无CR,1例PR,4例MR,6例SD,9例PD。总有效率为25%;对照组中无CR、PR、MR,6例SD,14例PD,总有效率为0%,两组有显著性差异（P〈0.05）。治疗组中位生存期为6.5个月,对照组中位生存期为2.5个月（P〈0.05）;治疗组TTP为3.5个月,对照组1.5个月（P〈0.05）;治疗组较对照组患者的AFP水平明显下降（P〈0.05）,生活质量有明显提高,上消化道出血的发生率降低（P〈0.05）。结论：奥曲肽治疗晚期原发性肝癌能有效延长患者的生存期,提高生活质量。     

Pre-clinical comparison of [DTPA0] octreotide, [DTPA0,Tyr3] octreotide and [DOTA0,Tyr3] octreotide as carriers for somatostatin receptor-targeted scintigraphy and radionuclide therapy

We have evaluated the potential usefulness of radiolabelled [DTPA⁰,Tyr³]octreotide and [DOTA⁰,Tyr³]octreotide as radiopharmaceuticals for somatostatin receptor–targeted scintigraphy and radiotherapy. In vitro somatostatin receptor binding and in vivo metabolism in rats of the compounds were investigated in comparison with [¹¹¹In-DTPA⁰] octreotide. Comparing different peptide–chelator constructs, [DTPA⁰,Tyr³]octreotide and [DOTA⁰, Tyr³]octreotide were found to have a higher affinity than [DTPA⁰]octreotide for subtype 2 somatostatin receptors (sst₂) in mouse AtT20 pituitary tumour cell membranes (all IC₅₀ values obtained were in the low nanomolar range). In vivo studies in CA20948 tumor-bearing Lewis rats revealed a significantly higher uptake of both ¹¹¹In-labelled [DOTA⁰,Tyr³]octreotide and [DTPA⁰,Tyr³]octreotide in sst₂-expressing tissues than after injection of [¹¹¹In-DTPA⁰]octreotide, showing that substitution of Tyr for Phe at position 3 in octreotide results in an increased affinity for its receptor and in a higher target tissue uptake. Uptake of ¹¹¹In-labelled [DTPA⁰]octreotide, [DTPA⁰,Tyr³]octreotide and [DOTA⁰,Tyr³]octreotide in pituitary, pancreas, adrenals and tumour was decreased to less than 7% of control by pre-treatment with 0.5 mg unlabelled octreotide/rat, indicating specific binding to sst₂. Comparing different radionuclides, [⁹⁰Y-DOTA⁰,Tyr³]octreotide had the highest uptake in sst₂-positive organs, followed by the [¹¹¹In-DOTA⁰,Tyr³]octreotide, whereas [DOTA⁰, ¹²⁵I-Try³]octreotide uptake was low compared to that of the other radiopharmaceuticals, when measured 24 hr after injection. Renal uptake of ¹¹¹In-labelled [DTPA⁰]octreotide, [DTPA⁰, Tyr³]octreotide and [DOTA⁰,Tyr³]octreotide was reduced over 50% by an i.v. injection of 400 mg/kg d-lysine, whereas radioactivity in blood, pancreas and adrenals was not affected. Int. J. Cancer 75:406–411, 1998. © 1998 Wiley-Liss, Inc.     

Treatment of a malignant enterocutaneous fistula with octreotide acetate.

An enterocutaneous malignant fistula developed in a patient who had a retroperitoneal angiosarcoma. He was treated with octreotide acetate subcutaneously. Drainage decreased and ceased after 2 weeks of therapy. The closure of this malignant fistula suggests that palliative therapy with octreotide acetate merits further study in view of the grave prognosis of this complication.