Effects of ligand priming and multiple-dose injection on tissue uptake of In-pentetreotide in rats

In patients undergoing somatostatin receptor scintigraphy, treatment with octreotide (Sandostatin^®) is usually discontinued 24–48 h before and after injection with the radioligand ¹¹¹In-pentetreotide ([¹¹¹In-DTPA^o]octreotide) (Octreoscan^®) because octreotide competes with radioligand for the same receptors. However, Dörr et al. and Soresi et al. reported improved visualization of carcinoid and small cell lung cancer lesions, respectively, during continued octreotide treatment. We found that intravenous administration of unlabeled octreotide to rats inhibited the binding of an optimal dose (0.5 μg) of ¹¹¹In-pentetreotide to somatostatin receptors in pancreas and adrenals in a mass- and time-dependent way. Pretreatment with unlabeled octreotide never increased receptor binding of ¹¹¹In-pentetreotide. Administration of 100 μg of octreotide decreased receptor-bound radioactivity if given simultaneously with or 10 or 20 min after injection of the radioligand, but had no effect if given 30 min after the radioligand. These findings indicate rapid processing of receptor-bound octreotide and suggest that octreotide treatment of patients undergoing ¹¹¹In-pentetreotide scintigraphy may be reinitiated as soon as 1 h after radioligand administration.     

Somatostatin receptor imaging in patients with sarcoidosis

Granulomatous diseases can be visualized in vivo after the injection of indium-111-DTPA-octreotide (¹¹¹In-pentetreotide), a radiolabelled somatostatin analogue. We evaluated whether somatostatin receptor imaging reflects disease activity, whether certain scintigraphic characteristics can predict the disease prognosis and whether repeat scintigraphy correlates with the clinical course in patients with sarcoidosis. ¹¹¹In-pentetreotide was injected in 46 patients and images were obtained 24 h later. Known mediastinal, hilar and interstitial disease was recognized in 36 of 37 patients. Also, such pathology was found in seven other patients who had normal chest X-rays. In five of these, somatostatin receptor imaging pointed to interstitial disease. Frequently, accumulation of radioactivity in parotid glands and supraclavicular lymph nodes was found. Neither the degree of radioactive accumulation in the thorax nor a specific pattern of pathological uptake was correlated with disease severity or clinical course. The degree of uptake of radioactivity in the parotid glands was correlated with significantly higher serum angiotensin-converting enzyme (ACE) levels. Somatostatin receptor imaging was repeated in 13 patients. In five of six patients in whom chest X-ray monitored improvement of disease activity, the pentetreotide scintigram also showed a decrease in pathological uptake. In two of five patients in whom the chest X-ray was unchanged, but serum ACE concentrations had decreased and lung function improved, normalization on pentetreotide scintigrams was found. It is concluded that: (1) somatostatin receptor imaging can demonstrate active granulomatous disease in patients with sarcoidosis; (2) pathological uptake of radioactivity in the parotid glands during somatostatin receptor imaging is correlated with higher serum ACE concentrations; (3) the value of somatostatin receptor imaging in the follow-up of patients with sarcoidosis will have to be determined in a prospective longitudinal study. Received 17 March and in revised form 17 April 1998     

Improved visualization of carcinoid liver metastases by indium-111 pentetreotide scintigraphy following treatment with cold somatostatin analogue

Five patients with hepatic metastases of midgut carcinoid underwent somatostatin receptor scintigraphy with indium-111 pentetreotide before and during treatment with octreotide. Octreotide treatment changed the biodistribution of ¹¹¹In-pentetreotide significantly. Whereas the radioactivity in liver, spleen and kidney decreased, hepatic metastases showed increased contrast. In one patient, liver metastases could only be detected during octreotide treatment. These data suggest that the diagnostic reliability of somatostatin receptor scintigraphy in carcinoid liver metastases is not necessarily compromised by octreotide therapy. Because of different biodistributions, the detection of liver metastases may even be improved during octreotide therapy. Correspondence to: U. Dörr     

和宁治疗上消化道大出血的临床研究

目的观察上消化道大出血40例用国产生长抑素（和宁）的治疗效果。方法治疗组40例先用5％葡萄糖20ml加和宁250μg静注,继而以250μg／h滴注,出血停止48h后停用。对照组36例先用5％葡萄糖20ml加垂体后叶素6U静注,继而以0．2U／min的速度持续滴注,出血停止48h后停用。通过胃管观察各组的止血效果,并观察药物不良反应。结果治疗组及对照组治疗总有效率分别为87．5％、55．6％,不良反应发生率分别为12．5％、63．89％,两组比较差异有统计学意义（P〈0．05）。结论和宁止血率高,不良反应少,是治疗各种原因所致上消化道大出血的首选药物。     

Radioiodinated somatostatin analogue RC-160: preparation,biological activity,in vivo application in rats and comparison with [123I-Tyr3]octreotide

We have evaluated the potential usefulness of the radioiodinated octapeptide RC-160, a somatostatin analogue, which might serve as a radiopharmaceutical for the in vivo detection of somatostatin receptor-positive tumours. For this purpose, iodine-123 and iodine-125 labelled RC-160 was tested for biological activity and applied in vivo in rats bearing the transplantable rat pancreatic tumour CA20948, which expresses somatostatin receptors. Our group has recently described the in vivo visualization of such tumours in rats and in humans with the radioiodinated somatostatin analogue [Tyr³]octreotide. Like [¹²³I-Tyr³]octreotide, ¹²³I-RC-160 showed uptake in and specific binding in vivo to somatostatin receptor-positive organs and tumours. However, blood radioactivity (background) was higher, resulting in a lower tumour to blood (background) ratio. We therefore conclude that in this animal model ¹²³I-RC-160 has no advantage over [¹²³I-Tyr³]octreotide as a radiopharmaceutical for the in vivo use as a somatostatin receptor imager, although, like [¹²³I-Tyr³]octreotide, ¹²³I-RC-160 shows specific binding to different somatostatin receptor-positive organs. Recently differences were reported in affinity between somatostatin and its analogues for somatostatin receptors expressed in different human cancers, like those of the breast, ovary, exocrine pancreas, prostate and colon. Therefore ¹²³I-RC-160 might be of interest for future use in humans as a radiopharmaceutical for imaging octreotide receptor-negative tumours. Correspondence to: W.A.P. Breeman, Department of Nuclear Medicine, University Hospital Dijkzigt, Dr. Molewaterplein 40, NL-3015 GD Rotterdam, The NetherlandsThe authors wish to thank Dr. Wil Kort, Ineke Hekking-Weyma, Reno Mekes, Marcello Harms and Ina Loeve for their expert assistance during the experiments.     

Somatostatin receptor scintigraphy using [111In-DTPA0]RC-160 in humans: a comparison with [111In-DTPA0]octreotide

Somatostatin receptor-positive lesions can be visualized by scintigraphy using [¹¹¹In-DTPA⁰]octreotide. Recently, there have been reports of differences in receptor binding between somatostatin receptor subtypes and between somatostatin analogues, such as RC-160 and octreotide, as well as of differences in internalization between the somatostatin receptor subtypes. The possibility that certain somatostatin receptor-positive tissues and tumours which do not bind octreotide may bind and internalize RC-160 would open new scintigraphic or radiotherapeutic applications of radiolabelled RC-160. We investigated the metabolism and tissue distribution of [¹¹¹In-DTPA⁰]RC-160 in comparison with [¹¹¹In-DTPA⁰]octreotide in four patients after injection of 250 MBq (10 μg) of these radiopharmaceuticals. Patient 1 had a metastatic follicular thyroid carcinoma, patient 2 a metastatic medullary thyroid carcinoma, patient 3 tuberculosis and patient 4 an insulinoma. The plasma clearance of the [¹¹¹In-DTPA⁰]RC-160 was slower than that of [¹¹¹In-DTPA⁰]octreotide, with 5% and 2%, respectively, of the initial plasma radioactivity remaining at 10 h p.i. The urinary excretion of [¹¹¹In-DTPA⁰]RC-160 was initially also slower than that of [¹¹¹In-DTPA⁰]octreotide, but the cumulative excretion of radioactivity was not significantly different at 48 h p.i. Approximately 80% of injected radioactivity was cleared in the urine, while in one patient 20% of the injected dose was recovered in the faeces. The slower clearance of [¹¹¹In-DTPA⁰]RC-160 resulted in a higher background in all organs studied i.e. liver, spleen, kidneys and lungs, at 24 h p.i. Although the target to background ratio with [¹¹¹In-DTPA⁰]octreotide was higher, no differences were found between the two analogues with regard to their sensitivity in detecting lesions in these four patients. We conclude that although only four subjects were studied, [¹¹¹In-DTPA⁰]RC-160 does not appear to have additional value for scintigraphy and is associated with higher background activity. Received 20 October and in revised form 31 October 1997     

生长抑素类似物介导靶向显像及治疗的研究现状和进展

放射性核素标记生长抑素类似物对神经内分泌肿瘤进行靶向诊断和靶向治疗已得到临床广泛认可.大多数生长抑素类似物仅对生长抑素受体2具有较高的亲和力,限制了其在临床中的应用.新一代生长抑素类似物如:1,4,7,10-四氮杂环十二烷-N,N',N",N'"-四乙酸-1-萘丙氨酸-奥曲肽(DOTA-NOC)等,可与更多亚型的生长抑素受体结合且具有更高的亲和力,可由发射不同射线的多种核素标记,已引起广泛重视.该文在介绍常规生长抑素类似物的基础上,着重讨论新的生长抑素类似物、新的螯合剂、新的标记核素及其新的组合,展望生长抑素受体介导肿瘤显像及治疗的前景.     

Somatostatin receptor scintigraphy using <Superscript>99m</Superscript>Tc-EDDA/HYNIC-TOC in patients with medullary thyroid carcinoma

Purpose Several new somatostatin analogues have been developed for the diagnosis and therapy of different tumours. Since somatostatin receptors are often over-expressed in medullary thyroid carcinoma (MTC), the aim of our study was to evaluate the utility of scintigraphy with the somatostatin analogue ^99mTc-EDDA/HYNIC-TOC in MTC in comparison with other diagnostic techniques. Methods Forty-five patients with MTC, aged 14–83 years, were investigated. Scintigraphy using ^99mTc-EDDA/HYNIC-TOC (Tektrotyd) was performed 2 and 4 h post injection of 740 MBq (20 mCi) of the tracer. Other imaging techniques were also applied and analysed in individual cases (ultrasonography, computed tomography, ^99mTc(V)-DMSA, ¹³¹I-MIBG, ^99mTc-MDP, ¹¹¹In-DTPA-octreotide and ¹⁸F-FDG-PET) and compared with ^99mTc-EDDA/HYNIC-TOC. Results In group 1 (eight patients before thyroidectomy), uptake of the tracer was found in the primary tumours. In group 2 (six patients with remission), a false positive result was found in one patient; in the remaining five patients, no pathological foci were visualised. In group 3 (31 patients with post-surgical hypercalcitoninaemia), scintigraphy was true positive in 23 patients (74.2%): uptake in the thyroid bed was found in five patients, in the lymph nodes in 18 and in bone metastases in four. Using ^99mTc-EDDA/HYNIC-TOC scintigraphy, the overall sensitivity was 79.5%, specificity 83.3%, accuracy 80.0%, positive predictive value 96.9% and negative predictive value 38.5%. Conclusion ^99mTc-EDDA/HYNIC-TOC is clinically useful for scintigraphy in the follow-up of patients with MTC. It can be used in clinical practice for preoperative evaluation, for localisation of local recurrence or distant metastases and particularly for therapy decision making.     

生长抑素、铝碳酸镁联治急性出血糜烂性胃炎的价值探索

目的探讨生长抑素与铝碳酸镁联合治疗急性出血糜烂性胃炎的临床效果。方法选择2018年5月~2019年5月收治的急性出血糜烂性胃炎患者60例,按照随机数字表法分为两组,每组30例,对照组给予铝碳酸镁,观察组给予铝碳酸镁+生长抑素,两组比较临床疗效、症状消失时间、住院时间、生活质量评分。结果临床总有效率观察组为93.33%,高于对照组的70.00%(P<0.05)。黑便、大便潜血、腹痛等症状消失时间观察组与对照组相比更短,住院时间观察组与对照组相比也更短,治疗后生活质量评分观察组与对照组相比更高,P均<0.05。结论生长抑素与铝碳酸镁联合治疗急性出血糜烂性胃炎的疗效显著,可提升生活质量。     

Somatostatin receptor scintigraphy in forty-eight patients with the Zollinger-Ellison syndrome

In patients with the Zollinger-Ellison syndrome, which is either sporadic or integrated into multiple endocrine neoplasia type 1, accurate localization of all the tumours is difficult and may have therapeutic implications. In an attempt to improve this localization, somatostatin receptor scintigraphy using [¹¹¹In-DTPA-D-Phe¹]-octreotide was performed prospectively in 48 consecutive patients with the Zollinger-Ellison syndrome. Thirty of them had the sporadic type of this disease. Scintigraphic data were compared with data obtained by conventional imaging methods, and also, in 32 selected patients, with those obtained by endoscopic ultrasonography. Somatostatin receptor scintigraphy showed abnormal tracer uptake in 39 patients (81%), in whom it correctly identified 50 of the 60 tumoral sites (83%) previously localized by the other imaging methods. In 17 patients (35%) somatostatin receptor scintigraphy disclosed abnormal tracer uptake at 18 different tumoral sites: 14 were located in the abdomen, including four in the liver and eight in the duodenopancreatic area, and four outside the abdomen, including two in the mediastinum. Six of the ten tumoral sites which were not correctly identified by somatostatin receptor scintigraphy were located in the duodeno-pancreatic area. However, in the 20 patients for whom conventional techniques failed to visualize any tumour in the duodenopancreatic area, somatostatin receptor scintigraphy was positive in ten (50%) whereas endoscopic ultrasonography was only positive in five (25%). In our patients with the Zollinger-Ellison syndrome, somatostatin receptor scintigraphy appeared to be a useful new addition to the battery of tests used for tumour detection.     

Indium-111 octreotide scintigraphy in patients with bone tumours of the extremities

Radiolabelled somatostatin analogues are of potential value in the imaging of somatostatin receptor-positive tumours. Recently, somatostatin receptors have been demonstrated in the osteoblast precursor cells. In this preliminary study, we evaluated the uptake characteristics of indium-111 octreotide in two benign and two malignant bone tumours. Tracer accumulation was observed in all four cases, and overall lesion to background ratio (mean±SD) was 2.74±0.84 and 2.98±1.49 at 4 h and 24 h, respectively. There was no clear relationship between I¹¹¹In-octreotide accumulation and the benign or malignant nature of the tumour. In one patient, tracer uptake was inhibited by unlabelled octreotide administration. These results suggest that¹¹¹In-octreotide can be taken up by benign and malignant bone tumours. The inhibition of tumour uptake by treatment with cold octreotide supports the concept that specific uptake mechanisms are responsible for¹¹¹In-octreotide deposition by bone tumours.     

Changes in the expression of somatostatin receptor imaging following Y-90 lanreotide therapy for carcinoid tumor: a flare response?

A 53-year-old man with In-111 octreotide-positive metastatic hepatic carcinoid was referred for Y-90 lanreotide therapy. A diagnostic In-111 lanreotide scan, performed to assess suitability for therapy, showed less uptake in lesions compared with In-111 octreotide. After 3 therapy doses of Y-90 lanreotide, a repeat In-111 lanreotide scan showed intense uptake in old lesions, appearance of new lesions, and uptake in the spleen. This was associated with improvement in flushing and regression of liver size. Computed tomography scan showed stable disease. Increased expression of somatostatin receptors has been observed with In-111 octreotide but not with In-111 lanreotide. If this is a flare response, then pretreatment with "cold" lanreotide may be beneficial before Y-90 lanreotide therapy.     

Imaging of dopamine D2 and somatostatin receptors in vivo using single-photon emission tomography in a patient with a TSH/PRL-producing pituitary macroadenoma

A 28-year-old man with a thyroid stimulating hormone/prolactin (TSH/PRL)-secreting pituitary macroadenoma is discussed in relation to dopamine D₂ and somatostatin receptor single-photon emission tomography (SPET). The patient presented with decreased vision in the left eye as a result of a temporal visual field defect and with mild hyperthyroidism. Medical therapy was tried. A test dose of both octreotide and bromocriptine resulted in an acute reduction in serum levels of TSH, -subunits and PRL, whereas there was no response to TRIAC. Somatostatin and dopamine D₂ receptors were present on the tumour as visualised by SPET with the ligands indium-111 diethylene triamine penta-acetic acid (DTPA)-octreotide (¹¹¹In-SMS) and iodine-123 iodobenzamide (¹²³I-IBZM), respectively. Therefore, treatment with octreotide 150 g t.i.d. subcutaneously and bromocriptine 10 mg b.i.d. orally was given for > 12 and > 6 weeks, respectively. Following this treatment the visual defects disappeared, although tumour size, as measured by CT scanning, and serum TSH levels did not decrease. SPET with ¹¹¹In-SMS and ¹²³I-IBZM after therapy revealed no change or a possible increase in somatostatin receptor binding potential and a possible decrease in dopamine D₂ receptor binding potential. The lack of long-term effects of the medical treatment is discussed. It is concluded that a high somatostatin and dopamine D₂ receptor binding potential in vivo in a TSH/PRL-producing adenoma does not necessarily predict a successful outcome of medical treatment. Correspondence to: N.P.L.G. Verhoeff     

大黄联合生长抑素在重症胆管炎术后应用的研究

目的探讨大黄联合生长抑素应用于重症胆管炎术后患者的治疗及其对血清中细胞因子TNF-α、IL-6、IL-8水平的影响。方法将来自本院术后ICU住院的患者（57例）分不同治疗组。采用放射免疫学法测定血清中TNF-α、IL-6、IL-8水平,并评价各治疗组的病死率、治愈率、胃肠障碍缓解时间、肝肾功能的变化和平均住院时间。结果患者血清中细胞因子水平早期明显升高,治疗后各组的细胞因子水平下降,前后比较差异有统计学意义（P〈0.01）。大黄联用生长抑素组治疗后的胃肠障碍缓解时间、平均住院时间较其它两组缩短,治疗有效率增高（P〈0.05）。结论早期大黄联用生长抑素应用于重症胆管炎术后患者安全有效。     

Somatostatin analogue scintigraphy in carcinoid tumours

Scintigraphy with iodine-123 or indium-111 labelled somatostatin analogue (octreotide) was performed in 52 patients diagnosed as, suspected of, or at risk of having carcinoid tumours. In 32 of 37 (86%) patients in whom histologically proven carcinoids were still present, known tumour sites were visualized. Using ¹²³I-coupled octreotide, 24 of 40 (60%) known extrahepatic sites were visualized, whereas all of 12 (100%) extrahepatic lesions were visualized after injection of ¹¹¹In-coupled octreotide. Known liver metastases were not distinctly visualized with octreotide scintigraphy in 12 of 24 patients. In all but two of these cases, an even distribution of radioactivity in the liver was observed. This is most probably due to the fact that these liver metastases accumulated about as much radioactivity as does normal liver tissue. Previously unsuspected localizations or sites not recognized with other imaging techniques were found in 20 of the 37 patients. In 3 of 11 patients who were thought to have been surgically cured, and in 4 of 4 patients who were suspected of having carcinoids, octreotide scintigraphy showed abnormal accumulation of radioactivity. Histological or radiological evidence that additional sites noticed on octreotide scintigrams indeed represented tumour tissue was obtained in ten patients. Visualization of the carcinoids did not depend on the site of the tumour or on the presence or absence of hormonal hypersecretion, as measured by urinary 5-hydroxyindoleacetic acid and serum -subunit concentrations. Apart from its use for tumour localization, octreotide scintigraphy, in consequence of its ability to demonstrate somatostatin receptor positive tumours, could be used to select those patients with the carcinoid syndrome who are likely to respond favourably to octreotide treatment.Correspondence to: D.J. Kwekkeboom     

生长抑素联合泮托拉唑治疗非食管胃底静脉曲张性上消化道出血疗效观察

目的探讨生长抑素联合泮托拉唑治疗非食管胃底静脉曲张性上消化道出血的临床疗效。方法46例非食管胃底静脉曲张性上消化道出血患者随机分为观察组和对照组,观察组在使用泮托拉唑和血凝酶基础上加用生长抑素治疗,比较两组治疗效果。结果观察组疗效高于对照组。结论生长抑素联合泮托拉唑治疗非食管胃底静脉曲张性上消化道出血疗效确切,值得临床推广应用。     

Somatostatin receptor subtype 2-mediated uptake of radiolabelled somatostatin analogues in the human kidney

Purpose Renal irradiation is a dose-limiting factor in peptide receptor radionuclide therapy using radiolabelled somatostatin analogues. This irradiation is mainly caused by reabsorption of radiolabelled peptides in the proximal tubule. In the human kidney, somatostatin receptors are expressed in the vasa recta, tubuli and glomeruli. It is not clear to what extent these receptors contribute to the total kidney radioactivity uptake. Methods Retrospectively, [¹¹¹In-DTPA⁰]octreotide scans of ten selected patients with carcinoids (well-differentiated gastrointestinal endocrine tumour) with liver metastases were evaluated. For each patient, two scans were obtained: one scan was performed without (control) and one during treatment with unlabelled octreotide. Kidney, tumour, spleen and liver uptake was measured in both scans. Results The interval between the two scans per patient varied from 50 to 397 days. Octreotide treatment substantially lowered kidney [¹¹¹In-DTPA⁰]octreotide uptake in eight out of ten patients. Kidney uptake in all patients was reduced to 82%±15% of control, (p < 0.01). A correlation between kidney uptake and spleen uptake was found (r=0.67, p < 0.05). Serum creatinine was unchanged. Surprisingly, tumour and liver [¹¹¹In-DTPA⁰]octreotide uptake was not significantly influenced by unlabelled octreotide therapy, but spleen uptake was significantly lowered by treatment (30.6% of control, p < 0.002). Conclusion We conclude that the somatostatin receptor plays a role in the total renal uptake of radiolabelled somatostatin analogues. The long interval between scans might explain the finding that tumour and liver metastasis uptake of [¹¹¹In-DTPA⁰]octreotide was unchanged. Further studies are needed to confirm and eludicate the results of this study.     

A new radiolabelled somatostatin analogue [111In-DTPA-D-Phe1]RC-160: preparation,biological activity,receptor scintigraphy in rats and comparison with [111In-DTPA-D-Phe1]octreotide

We have evaluated the potential usefulness of indium-111 labelled [DTPA-D-Phe¹]RC-160, derived from the octapeptide somatostatin analogue RC-160, as a radiopharmaceutical for the in vivo detection of somatostatin receptor-positive tumours. For this purpose ¹¹¹In-and ¹¹¹In-labelled [DTPA-D-Phe¹]RC-160 was tested for its biological activity, and applied for somatostatin receptor scintigraphy in vivo to rats bearing the transplantable rat pancreatic tumour CA20948, which expresses somatostatin receptors. We previously described the development of the ¹¹¹In-labelled somatostatin analogue [DTPA-D-Phe¹]octreotide and its use in the in vivo visualization of somatostatin receptor-positive tumours in rats and in humans. Like [¹¹¹In-DTPA-D-Phe¹]octreotide, [¹¹¹In-DTPA-D-Phe¹]RC-160 showed uptake in and specific binding in vivo to somatostatin receptor-positive organs and tumours, and the tumours were clearly visualized by gamma camera scintigraphy. However, as compared to [¹¹¹In-DTPA-D-Phe¹]octreotide, blood radioactivity (background) was higher, resulting in a lower tumour to blood (background) ratio. Using this animal model we therefore conclude that [¹¹¹In-DTPA-DPhe¹]RC-160 has no advantage over [¹¹¹In-DTPA-DPhe¹]octreotide as a radiopharmaceutical in the visualization of somatostatin receptors which bind both analogues. However, recent reports suggest the existence of different somatostatin receptor subtypes on some human cancers, which differentially bind RC-160 and not octreotide. These tumours include cancers of the breast, ovary, exocrine pancreas, prostate and colon. [¹¹¹In-DTPA-D-Phe¹]RC-160 might be of interest for future use in such cancer patients as a radiopharmaceutical for imaging somatostatin receptor-positive tumours, which do not bind octreotide.     

Somatostatin receptor sst1-sst5 expression in normal and neoplastic human tissues using receptor autoradiography with subtype-selective ligands

Somatostatin receptors are known to be expressed in a large number of human tumours and represent the basis for in vivo tumour targeting. Stable somatostatin derivatives such as octreotide or lanreotide are the most frequently used radiopharmaceuticals acting through specific binding to somatostatin receptors; however, they do not bind with high affinity to all five receptor subtypes. Whereas the mRNAs for most receptor subtypes have been detected in tumours, it is in most cases unclear which of the receptor subtype proteins are expressed. Since in vitro receptor binding methods are close correlates and predictors of in vivo peptide receptor targeting, we took advantage of the recently developed subtype-selective analogues and evaluated approximately 200 tumours for their receptor subtype protein expression in specific binding assays using autoradiography with 125I-[Leu8, D-Trp22, Tyr25]-somatostatin-28 and displacement by subtype-selective analogues. The majority of the tested neuroblastomas, meningiomas, medulloblastomas, breast carcinomas, lymphomas, renal cell carcinomas, paragangliomas, small cell lung carcinomas and hepatocellular carcinomas predominantly expressed sst2. The prostate carcinomas and sarcomas preferentially expressed sstl, while a majority of inactive pituitary adenomas displayed sst3 and, to a lesser extent, sst2. Growth hormone-secreting pituitary adenomas preferentially expressed sst2 and sst5; gastroenteropancreatic tumours and phaeochromocytomas frequently displayed sst2 and/or sstl. Non-neoplastic human tissues such as vessels, nerve plexus, pancreatic islets, prostatic stroma, adrenal medulla, spleen and germinal centres of the lymphoid tissues preferentially expressed sst2. However, the human gastric mucosa predominantly expressed sst1 while colonic mucosa displayed sst2. Interestingly, a minority of tumours showed a strong 125I-[Leu8, D-Trp22, Tyr25]-somatostatin-28 binding, of which less than 50% could be displaced by the sum of the five subtype-selective analogues. This observation suggests the existence of an as yet unknown subtype in selected tumours. This study is the first report to analyse the somatostatin receptor subtype expression in tumours with binding methods. We conclude that sst2, with high affinity for current radiopharmaceuticals such as Octreoscan, is predominantly expressed in a majority of tumours. Fewer tumour types (sarcomas, prostate cancers, inactive pituitary adenomas) preferentially express another subtype. This information is of importance with regard to the clinical applications and development of somatostatin analogues with distinct receptor subtype selectivities.     

生长抑素类似物介导靶向显像及治疗的研究现状和进展

放射性核素标记生长抑素类似物对神经内分泌肿瘤进行靶向诊断和靶向治疗已得到临床广泛认可。大多数生长抑素类似物仅对生长抑素受体2具有较高的亲和力,限制了其在临床中的应用。新一代生长抑素类似物如:1,4,7,10-四氮杂环十二烷-N,N',N",N'"-四乙酸-1-萘丙氨酸-奥曲肽(DOTA-NOC)等,可与更多亚型的生长抑素受体结合且具有更高的亲和力,可由发射不同射线的多种核素标记,已引起广泛重视。该文在介绍常规生长抑素类似物的基础上,着重讨论新的生长抑素类似物、新的螯合剂、新的标记核素及其新的组合,展望生长抑素受体介导肿瘤显像及治疗的前景。