99mTc-depreotide生长抑素受体显像的临床应用研究

生长抑素受体显像近年来研究较多，depreotide已成为其研究热点之一。Depreotide在诊断与鉴别诊断临床常见的孤立性肺结节方面有其独特优势；此外，^99mTc—depreotide生长抑素受体显像在乳腺癌、甲状腺癌、淋巴瘤等肿瘤及甲状腺相关性眼病等非肿瘤性疾病也有一定应用前景。     

生长抑素受体显像剂 99Tcm-HTOC的制备

目的　研制99Tcm 标记的生长抑素受体 (SSTR)阳性肿瘤显像剂99Tcm 6 肼基烟酰基 [Tyr3] octreotide (HTOC)。方法　通过四步化学反应合成 ,HPLC纯化 ,得到HTOC ;用乙二胺 N ,N′ 二乙酸 (EDDA)作为配体进行99Tcm 标记 ,测定标记率与标记物稳定性。结果　所合成HTOC质谱的分子离子峰与HTOC相对分子质量一致 ,99Tcm HTOC标记率 >95 % ,标记后 6h放化纯仍 >95 %。结论该法研制的99Tcm HTOC标记率高 ,体外稳定性好。     

99Tcm-sandostatin生长抑素受体显像用于诊断肺癌

目的　探讨99Tcm sandostatin生长抑素受体显像对肺癌的诊断价值。方法　 35例肺部肿瘤患者静脉注射99Tcm sandostatin (991 6± 187 5 9)MBq后行平面及胸部断层SPECT显像 ,重建后获得发射 透射图像及融合图像。勾画感兴趣区 ,计算肿瘤和对侧正常肺组织的放射性比值 (T N)。所有病灶均经病理检查及 (或 )其他检查证实。 5例孤立性肺结节 (SPN)行1 8F 脱氧葡萄糖 (FDG)符合线路显像 ,1例小细胞肺癌 (SCLC)治疗前后均行99Tcm sandostatin显像。 15例受检者于99Tcm sandostatin显像后 1周内行全身骨显像。结果　99Tcm sandostatin显像诊断肺癌的灵敏度、特异性和准确性分别为 93 3%、5 5例和 94 3%。 2例鳞癌99Tcm sandostatin显像假阴性。 4例SCLC99Tcm sandostatin显像发现胸膜异常放射性浓聚区 ,病理检查证实为胸膜转移。15例骨显像中 12例发现骨转移 ,99Tcm san dostatin仅发现 5例骨转移。SCLC、非小细胞肺癌 (NSCLC)T N分别为 3 4 3± 0 6 6、2 2 4± 0 31,差异有显著性 (t=4 0 72 ,P <0 0 0 1)。SCLC对99Tcm sandostatin的摄取明显高于NSCLC。结论　99Tcm san dostatin生长抑素受体显像无创、安全、经济 ,对肺癌有较好的诊断价值。     

肿瘤生长抑素受体显像剂~(99)Tc~m-octreotide的制备及鉴定

目的　建立99Tcm 直接标记octreotide的最佳方法 ,评价其受体介导结合特性以及作为肿瘤生长抑素受体显像剂的可能性。方法　采用抗坏血酸钠和连二亚硫酸钠作为还原剂 ,对oct reotide进行标记 ;用大鼠脑皮质细胞膜进行体外受体结合分析 ;进行动物体内分布、药代动力学、毒性实验和临床受体显像。结果　99Tcm octreotide放化纯达 78 5 % ,纯化后为 93 8% ,室温下放置 4h为92 1%。细胞膜体外放射受体结合分析证实99Tcm octreotide与octreotide具有相同的受体介导结合特性。 3例肺癌患者临床受体显像均获得阳性结果。结论　99Tcm 直接法标记octreotide方法可行 ,稳定性好 ;99Tcm octreotide是一种很有希望的肿瘤生长抑素受体显像剂     

生长抑素受体肿瘤显像的临床应用及研究进展

神经内分泌肿瘤及一些非神经内分泌肿瘤细胞表面均有生长抑素受体高表达。生长抑素类似物如奥曲肽等对生长抑素受体具有亲和力高、作用时间长等特点,并可被放射性核素标记进行肿瘤阳性显像,这对生长抑素受体阳性肿瘤的诊断、分期及预后评价具有较为重要的临床价值,也可作为常规影像学检查的一种有力补充。     

99mTc-Sandostatin诊断高表达生长抑素受体的胰腺癌的实验研究

胰腺癌发病率在全身各恶性肿瘤中仅次于肺癌、肠癌和乳腺癌,占第4位.胰腺癌早期诊断困难,常用的影像学检查改变不明显.本研究自制99mTc-Sandostatin对荷胰腺癌裸鼠模型行SSR显像,探讨99mTc-Sandostatin显像诊断胰腺癌的可能性及与肿瘤组织SSR表达水平的关系.     

^99mTc标记生长抑素类似物作为受体显像剂及其特性研究

简述放射性碘（＾１２３Ｉ、１２５Ｉ和１３１Ｉ）、￣１１１Ｉｎ和＾９９ｍＴｃ标记生长抑素类似物的方法及其优缺点，重点叙述＾９９ｍＴｃ的标记方法（直接法、间接法和环状肽标记法）和＾９９ｍＴｃ标记生长抑素类似物有关特性研究及临床应用的进展。     

^99Tc-Sandostatin诊断高表达生长抑素受体的胰腺癌的实验研究

胰腺癌发病率在全身各恶性肿瘤中仅次于肺癌、肠癌和乳腺癌,占第4位.胰腺癌早期诊断困难,常用的影像学检查改变不明显.本研究自制99mTc-Sandostatin对荷胰腺癌裸鼠模型行SSR显像,探讨99mTc-Sandostatin显像诊断胰腺癌的可能性及与肿瘤组织SSR表达水平的关系.     

肿瘤生长抑素受体显像剂^99Tc^m—octreotide的制备及鉴定

目的 建立＾９９Ｔｃ＾ｍ直接标记ｏｃｔｒｅｏｔｉｄｅ的最佳方法,评价其受体介导结合特性以及作为肿瘤生长抑素受体显像剂的可能性。方法 采用抗坏血酸钠和连二亚硫酸钠作为还原剂,对ｏｃｔ－ｒｅｏｔｉｄｅ进行标记;用大鼠脑皮质细胞膜进行体外受体结合分析;进行动物体内分布、药代动力学、毒性实验和临床受体显像。结果 ＾９９Ｔｃ＾ｍ－ｏｃｔｒｅｏｔｉｄｅ放化纯达７８．５％,纯化后为９３．８％,室温下放置４ｈ为９     

肺腺癌摄取骨显像剂99mTC-MDP一例

骨外组织(包括肺癌组织)摄取骨显像剂99mTC-MDP曾有报道[1-5],但肺腺癌摄取99mTC-MDP,尚无报道,现将本例报告如下:1临床资料患者,女性,69岁。主因“胸痛”并胸透发现右肺阴影,于2004年7月24日入院。胸部CT示:右肺下叶致密肿块,大小为5.0 cm×2.8 cm,肿块累及胸膜,边缘清晰,并见浅分叶征,未见胸水;同时,在CT引导下,行胸穿取肺组织活检,病理结果示:低分化腺癌,免疫组化示:CK7( )、CK14(-);核素全身骨扫描示:前位及后位,在第8、9肋骨处,均有局限性放射性浓聚,两者相比较,后位较前位浓;SPECT胸部断层发现,在右肺中下部靠近后胸部有…     

Oestrogen-mediated regulation of somatostatin receptor expression in human breast cancer cell lines assessed with 99mTc-depreotide

Investigating three somatostatin receptor (SSTR)-positive (+) human breast cancer cell lines, Xu et al. found a time- and dose-dependent up- or down-regulation of SSTR2 mRNA expression by 17-oestradiol (E₂) or the anti-oestrogen tamoxifen, respectively, in the two oestrogen receptor-positive (ER+) cell lines but not in the oestrogen receptor-negative (ER–) cell line. This study aimed to confirm the findings of Xu et al. at the protein level by means of western blotting and saturation binding studies using ^99mTc-depreotide (NeoSpect). The ER+/SSTR+ ZR75-1 and T47D and SSTR+/ER– MDA MB231 breast cancer cell lines were exposed to 1 nM E₂ or a combination of 1 nM E₂ plus 100 nM tamoxifen or ICI 182 780 (Faslodex) for 48 h. Exposed and non-exposed controls were incubated with increasing concentrations of ^99mTc-depreotide (0.5 nM–15 nM) in the absence and the presence of 20 M of octreotide. Scatchard-Rosenthal plots were derived using commercially available software. SSTR subtypes responsible for E₂-induced changes in ^99mTc-depreotide binding were identified by means of western blotting. Mean K_d values for ^99mTc-depreotide were 13 nM, 7 nM and 4 nM for T47D, ZR75-1 and MDA MB231 cells, respectively. After stimulation with E₂, the ER+ cell line T47D demonstrated a mean increase of 81% (P<0.05) in ^99mTc-depreotide binding. Adding the partial agonist tamoxifen and full antagonist ICI 182 780 to E₂ blocked the induced increase in T47D cells, either reducing SSTR expression or restoring it to control levels. ZR75-1 cells stimulated with E₂ showed a mean decrease in ^99mTc-depreotide binding of 36% as compared to control cells; this difference, however, proved to be not statistically significant. Similarly, B_max values did not change in ZR75-1 cells exposed to E₂ in combination with an ER antagonist as compared to control cells. Finally, no influence of E₂ on ^99mTc-depreotide binding was observed in the ER– cell line MDA MB231. Both SSTR2 and SSTR5 were expressed at high levels in T47D cells and ZR75-1 cells. SSTR5 drastically increased in the absence of E₂ and was restored to the original detection level after E₂ treatment. The presented findings support an oestrogen-dependent regulation of SSTR expression in breast cancer cell lines.     

Technetium-99m dextran: a promising new protein-losing enteropathy imaging agent

The purpose of this study was to evaluate technetium-99m dextran (^99mTc-Dx; molecular weight 81000) as a prospective protein-losing enteropathy (PLE) imaging agent. Twenty-two patients with diseases commonly associated with PLE and 12 healthy control subjects underwent intravenous^99mTc-Dx scintigraphy. All of the 22 test patients showed significant radiotracer accumulation in the intestines within 3–4 h post injection. The focal, regional or generalised nature of the enteropathy and involvement of the large or small intestine could be identified in most cases. Four of the 12 apparently healthy subjects also showed minimal accumulation in the abdominal area occurring late in the study period. This could have been physiological, related to food habits or due to unsuspected intestinal worms. We attribute the high sensitivity of^99mTc-Dx to its relatively fast blood (background) clearance. The radiotracer may have several other advantages over^99mTc-labelled human serum albumin in imaging PLE.     

Technetium-99m ethylene dicysteine: a new renal tubular function agent

Technetium-99m ethylene dicysteine (EC), a metabolite of ethylene cysteine dimer (ECD), is a new technetium-labelled renal tubular function tracer introduced as an alternative to ortho-iodohippurate (OIH) and with imaging qualities similar to 99mTc-mercaptoacetyltriglycine (MAG3). The elimination of ^99mTc-EC is principally via active tubular transport. It is available in lyophilised kit form which can be easily prepared at room temperature, and the compound remains stable for at least 8 h. Both in normal individuals and in patients, plasma clearance of ^99mTc-EC has been reported to be around 0.75 of OIH clearance. Thus there is a very strict correlation between ^99mTc-EC and OIH clearance, and several algorithms are available to estimate OIH clearance from ^99mTc-EC clearance. The renal extraction ratio of ^99mTc-EC is 0.70. The distribution volume of ^99mTc-EC is twice that of ^99mTc-MAG3 (20% of body weight) and slightly higher than that of OIH. The plasma protein-bound fraction of ^99mTc-EC (30%) is significantly lower than that of ^99mTc-MAG3 and OIH. The same applies to red blood cell binding of ^99mTc-EC (5.7%). There is negligible uptake in the liver and intestines. Within 1 h 70% of ^99mTc-EC is excreted in the urine. ^99mTc-EC provides the same scintigraphic information as ^99mTc-MAG3. The lower liver activity makes ^99mTc-EC particularly attractive in patients with renal failure. The ^99mTc-EC clearance can be accurately estimated from a single plasma sample obtained at 54 min after injection. In conclusion, ^99mTc-EC is a suitable renal imaging agent and for some applications is even more attractive than OIH: it provides an index of tubular function and yields high-quality images. The labelling procedure is easy, radiochemical purity is high and the complex is stable for a long time. The extent to which ^99mTc-EC is adopted for clinical use will ultimately depend upon its cost and availability.     

Imaging of regional lymph node metastases with 99mTc-depreotide in patients with lung cancer

Purpose The aim of this study was to evaluate the clinical usefulness of scintigraphy with ^99mTc-depreotide in the assessment of loco-regional nodal spread in patients with suspected lung cancer in comparison with computed tomography (CT).Methods Eighty-six patients were investigated with single-photon emission computed tomography (SPECT) of the thorax after i.v. injection of 740 MBq ^99mTc-depreotide. The results were evaluated in conjunction with a thoracic CT scan in all 86 patients with 204 lymph node stations. The scintigraphic results were correlated with cytological (38), histological (20) or clinical–radiological (146) findings and compared with CT. The quantitative evaluation of depreotide uptake was performed on 48 cytologically or histologically verified nodal stations from 28 patients by SPECT using region of interest analysis with four different reference regions.Results ^99mTc-depreotide scintigraphy for all 204 investigated lymph node stations had a sensitivity of 99% and a negative predictive value of 98% in determining lymph node involvement. Scintigraphy and CT showed the same level of accuracy, 76.4%. CT findings had a higher positive predictive value but a lower negative predictive value compared to ^99mTc-depreotide scintigraphy. The quantitative evaluation of depreotide uptake in lymph nodes using vertebra as a reference region showed that a cut-off level of 0.56 excludes malignant involvement of lymph nodes, while a cut-off level of 1.66 excludes benign disease in lymph nodes. About 73% of all investigated lymph node stations showed uptake values between these cut-off levels.Conclusion Absence of ^99mTc-depreotide uptake on scintigraphic imaging can exclude regional lymph node involvement with a high degree of probability and may be useful in clinical practice. The quantitative evaluation of depreotide uptake in regional lymph nodes did not increase the diagnostic accuracy of the method in general but did elucidate the lymph node status in some patients.     

Evaluation of 99mTc-dextran as a lymphoscintigraphic agent in rabbits

Dextran (clinical grade, average mol. wt. 82,200) was labelled with ^99mTc and the labelling efficiency was checked by paper and thin-layer chromatography and electrophoresis. The amount of free ^99mTcO ₄ ^- was always less than 1%. The radiopharmaceutical was injected ID into the web space in hind legs of ten rabbits (200–600 Ci/0.05 ml). Scintigrams were taken at 10-min intervals up to 3 h in three rabbits. The injection site and the hind legs were massaged after injection in the other seven rabbits and scintigrams were taken at 10-min intervals up to 2 h. Blood samples were obtained at 5, 15, 30, 90 and 120 min in both groups. In addition a 180-min sample, was also taken in the first group. At the end of the study the rabbits were killed and the popliteal lymph nodes and the organs were removed to be weighed, and counted. Our results indicated a high concentration of radioactivity in the popliteal lymph nodes and massage at the injection site increased the average uptake of the popliteal lymph node from 1.12%±0.77% to 4.28%±1.57% at 3 and 2 h, respectively (P<0.001). In scintigrams the lymph channels and the nodes were very well visualised. The blood radioactivity levels were too low to present a background problem. With massage 30% of the injected dose was removed from the injection site in 2 h. We have shown that ^99mTc-dextran is a good radiopharmaceutical for the visualisation of the lymph system and deserves further experimental and clinical studies.     

The role of 99mTc-depreotide in the management of neuroendocrine tumours

BACKGROUND: In-pentetreotide scan (OctreoScan) is a widely available agent with high sensitivity for imaging neuroendocrine tumours. Negative In-pentetreotide poses diagnostic as well as therapeutic problems in terms of staging and consideration of targeted radionuclide therapy. AIM: To assess the role of Tc-depreotide in patients with negative or weakly positive OctreoScan (Krenning score< or =1; measured on a scale range 0-4). To determine the usefulness of Tc-depreotide scintigraphy for highlighting lesions that may be missed by OctreoScan and/or CT/MRI imaging. STUDY DESIGN: Prospective analysis of 25 patients with neuroendocrine tumours, with negative or weakly positive In-pentetreotide scans, who were consecutively enrolled to undergo In-pentetreotide and Tc-depreotide imaging. The results were compared with either CT or MRI scans. RESULTS: Histology was available for 20 of 25 patients: of these 40% had high-grade tumours (cellular proliferation marker Ki-67 score >20%), a further 35% had intermediate-grade tumours (Ki-67 2-20%), and the remaining 25% had low-grade tumours (Ki-67 <2%). Fifty-two percent of patients had completely negative and 48% had weakly positive OctreoScan results. Thirty-two percent of these same patients had significantly positive Tc-depreotide scans (Krenning score> or =2), with the histology demonstrating intermediate-grade or high-grade tumours. CONCLUSION: Tc-depreotide imaging has low sensitivity but is useful in a one-third of OctreoScan-negative patients, displaying significantly better uptake than In-pentetreotide in this patient group. It aids diagnosis by highlighting lesions not seen by OctreoScan and/or CT/MRI imaging, and can possibly identify a group of patients amenable to therapy with radionuclide agents, such as SOM230, targeting somatostatin receptor subtypes 2, 3 and 5.     

99mTc-Diethyl-iodo-HIDA (JODIDA): A new hepatobiliary agent in clinical comparison with 99mTc-diisopropyl-HIDA (DISIDA) in jaundiced patients

The new HIDA derivative, ^99mTc-dimethyl-iodine-HIDA (JODIDA), was compared with ^99mTc-diisopropyl-HIDA (DISIDA) in 17 patients with jaundice by means of paired cholescintigraphic imaging studies. The following parameters were visually assessed: the extent of urinary tract visualization, biliary contrast and appearance time, and gallbladder visualization and appearance time. In the 6 patients with a total bilirubin level of between 19 and 66 mol/l (1.1 and 3.9 mg/dl), both radiopharmaceuticals gave similar results except for the moderate visualization of the urinary tract with DISIDA in contrast to JODIDA. In the remaining 11 patients with a total bilirubin level between 102 and 1303 mol/l (6 and 76 mg/dl), JODIDA showed significant advantages over DISIDA: non-visualization of the urinary tract, stronger and faster biliary contrast, and better gallbladder visualization. JODIDA thus offered substantial diagnostic advantages over DISIDA in 8 of these patients. In 4 patients, the differential diagnosis of jaundice (intrahepatic or mechanical disorder) was possible with JODIDA, whereas DISIDA either could not visualize intestinal or gallbladder activity at all or could not differentiate it from the urinary tract. In one patients, JODIDA offered faster (18 h) diagnosis. In the remaining 3 patients, other, substantially false interpretations could be avoided through the use of JODIDA. Further clinical experience with JODIDA in more than 40 patients confirmed the results of this study. We concluded that JODIDA is of significant advantage over DISIDA in clinical situations such as total bilirubin level above 80–100 mol/l (4.7 to 5.8 mg/dl), examination of small children and critically ill patients and suggestion of bile leakage. As there are also no clinical disadvantages, it could become the rediopharmaceutical of choice for hepatobiliary imaging.     

First evaluation of technetium-99m dimercaptopropionyl albumin as a possible tracer agent for ventriculography in a volunteer

Technetium-99m labelled red blood cells (^99mTc-RBCs) are the standard radiopharmaceutical for radionuclide ventriculography but suffer from some practical disadvantages such as risk of viral contamination and lengthy preparation (in vitro labelling) or poor labelling efficiency due to patient medication interactions (in vivo labelling). ^99mTc-labelled human serum albumin (HSA) is not really a valuable alternative as the activity diffuses too rapidly out of the vascular space due to the weak binding of the radionuclide. We have modified HSA by reaction with N-hydroxysuccinimidyl 2,3di(S-acetylmercapto)propionate (SAMP) to introduce a varying number of 2,3-dimercaptopropionyl (DMP) side chains. The resulting DMP-HSA can be rapidly labelled with ^99mTc at room temperature by simple addition of stannous ions and eluate of a ^99mTc generator. After evaluation in mice and rabbits, two different ^99mTc-DMP-HSA preparations — obtained after reaction of SAMP with albumin in a molar ratio of, respectively, 8:1 and 16:1 — were tested in a volunteer and compared to ^99mTcRBCs. The blood time-activity curves of the three preparations were quite similar but both ^99mTc-DMP-HSA preparations were excreted much less into the urine than ^99mTc-RBCs. Ventriculography was performed with the three tracer agents, each time with a 1-week interval. In the three studies, the heart was clearly visualized and the left and right ventricle could be easily delineated. The ejection fractions obtained after administration of the three preparations were similar. With both ^99mTc-DMP-HSA preparations the low activity in the spleen was a distinct advantage and facilitated delineation of the left ventricle. However, a slightly higher liver uptake was seen with ^99mTc-DMP-HSA 16:1, whereas the liver uptake of ^99mTc-DMP-HSA 8:1 and ^99mTc-RBCs was the same. These first results suggest that ^99mTc-DMP-HSA, and in particular ^99mTc-DMP-HSA 8:1, could be used for ventriculography as a practical and reliable alternative to ^99mTc-RBCs.     

新型心肌显像剂[99Tcm(N)(PNP5)(DBODC)]+猪心肌显像研究

目的 评价新型心肌显像剂[99Tcm(N)(PNP=5)(DBODC)]+在猪体内的药代动力学特征及生物分布特性.方法 利用药盒法制备[99Tcm(N)(PNP5)(DBODC)]+注射液.实验动物选7头实验用成年健康中华小型猪,由耳静脉注入[99Tcm(N)(PNP5)(DBODC)]+,分别于注射后2,5,10,15,30,45,60,75,90,120,150和180 min从猪后肢静脉进行血样采集以获得药代动力学参数,同时进行胸腹部平面系列显像,以观察该药物在猪体内的生物分布和靶/非靶比值,并与99Tcm-甲氧基异丁基异腈(MIBI)显像比较(采用配对t检验).结果 [99Tcm(N)(PNP5)(DBODC)]+标记率为(95.54±0.85)%,其符合一次静脉给药的药代动力学二室模型,分布半衰期T1/2á=(2.97±0.48)min,消除半衰期T1/2a=(52.49±19.49)min,血液总清除速率(CL)=(14 314.29.±8445.79)ml/h.心、肝、肺时间-放射性曲线显示[99Tcm(N)(PNP5)(DBODC)]+肝摄取在初始时明显高于心肌,但肝内放射性清除迅速,在注射30 min后,肝内放射性已低于心肌放射性,而99Tcm-MIBI肝摄取在180 min内均高于心肌.[99Tcm(N)(PNT5)(DBODC)]+的心/肝比值在注射后30～180 min均高于99Tcm-MIBI(t值为10.395～54.482,P均＜0.05).显像示在注射[99Tcm(N)(PNP5)(DBODC)]+后5～180 min均可获得清晰的心肌图像,肝内示踪剂迅速排入胆、肠系统,致使肝内放射性迅速减低,有利于减少对左室下壁的干扰.结论 [99Tcm(N)(PNP5)(DBODC)]+有望成为一种新的心肌灌注显像剂.