氯胺酮镇痛作用与3种受体的关系

目的 探讨氯胺酮镇痛作用与N-甲基-D-天冬氨酸(NMDA)受体、阿片受体、甘氨酸受体的关系,阐明氯胺酮的镇痛作用靶点.方法 将480只小鼠随机分成3大组(NMDA组、纳络酮组和士的宁组),分别进行扭体法和热板法实验,每组160只小鼠随机分为空白组和氯胺酮组,每组再分为8小组(n=10).NMDA组:空白组鞘内注射人工脑脊液(aCSF)或2.5、5、10ng NMDA(NMDA用aCSF稀释),均10μl,注射时间为10s;氯胺酮组均腹腔注射氯胺酮20mg/kg,5min后分别鞘内注射acsF 10μl或2.5、5、10ng NMDA.纳络酮组和士的宁组:动物分组与用药(纳络酮或士的宁)方法同NMDA组.通过扭体法实验分别观察鞘内注射NMDA、腹腔注射纳络酮和士的宁对腹腔注射0.6%冰醋酸溶液(10ml/kg)的小鼠15min内扭体次数的影响.通过热板法观察小鼠用药前、用药后5、10、15、20、30min的热板法痛阈(HPPT).结果 NMDA对空白组小鼠HPPT及扭体次数均无明显影响(P＞0.05),但可增加氯胺酮组小鼠的扭体次数(P＜0.05),缩短其HPPT(P＜0.01).腹腔注射纳络酮(1、2、4mg/kg)或士的宁(0.25、0.5、0.75μg)对空白组小鼠HPPT、扭体次数和氯胺酮组小鼠的扭体次数均无明显影响(P＞0.05),但可缩短氯胺酮组小鼠的HPPT(P＜0.05,P＜0.01).结论 氯胺酮对热刺激的镇痛作用与NMDA受体、阿片受体、甘氨酸受体有关,对化学刺激的镇痛作用与NMDA受体有关,而与阿片受体、甘氨酸受体关系不大.     

Disuse atrophy, plasma corticosterone, and muscle glucocorticoid receptor levels

A suspension model, characterized by differential atrophy of disused hindlimb skeletal muscles, was utilized to investigate plasma levels of and tissue sensitivity to glucocorticoids. The three objectives were determination of time course and extent of plasma corticosterone changes during 1 week of whole-body suspension; comparison of glucocorticoid receptor site concentrations in muscles differing in morphology and antigravity function; and investigation of the effect of disuse on tissue glucocorticoid receptor site concentrations. Plasma corticosterone increased significantly (p less than 0.01) on the first and third days of suspension, but returned to control levels by day 7. Muscle glucocorticoid receptors exhibited a characteristic hormonal specificity. In controls, receptor site concentration in the slow-twitch soleus (48 +/- 5 fmol/mg prot.) was comparable to that in the fast-twitch gastrocnemius (47 +/- 6) and plantaris (58 +/- 4) muscles but significantly (p less than 0.02) less than the extensor digitorum longus (66 +/- 5). Seven days of suspension resulted in significant differential effects on muscle receptor levels, with a large increase in the soleus (140%), lesser increments in the gastrocnemius (55%) and plantaris (45%), and only a small, statistically insignificant alteration in the EDL (10%). Receptor levels in the soleus remained elevated following 14 d of suspension, but levels in other muscles returned to control values. These results suggest that circulating glucocorticoids, as well as increased tissue hormonal sensitivity, may be related to muscle responses in this model of disuse.     

Chronic alcohol intake, resistance training, and muscle androgen receptor content

INTRODUCTION: Chronic alcohol intake and resistance training (RT) have opposite effects on muscle physiology. PURPOSE: This study examined the effect of chronic alcohol intake on androgen receptor (AR) content in skeletal muscle to determine whether this effect was influenced by RT. METHODS: A total of 48 male Sprague Dawley(R) rats (mass = 456 +/- 1 g; mean +/- SE) were divided into five groups: baseline (N = 8), sedentary + alcohol (Sed-Al) (N = 8), sedentary + normal diet (Sed-Nml) (N = 8), exercise + alcohol (Ex-Al) (N = 12), and exercise + normal diet (Ex-Nml) (N = 12). Exercise groups completed a 6 1/3-wk "squat" RT protocol; alcohol groups received an ethanol-rich (35% caloric content of alcohol) diet throughout the 6 1/3-wk period. Baseline animals were killed at the onset of the 6 1/3-wk training period. RESULTS: Western blot analysis showed no effect of alcohol or RT on the AR of the extensor digitorum longus. Alcohol significantly reduced AR content of the rectus femoris (P < 0.05) and prevented RT-induced increases in AR content of the soleus. CONCLUSION: Chronic alcohol intake appeared to reduce the AR content of the type IIB fiber-predominant rectus femoris, and this reduction was not affected by RT. In the type I-predominant soleus, chronic alcohol intake alone had no effect but seemed to prevent RT-induced increases in AR content.     

σ受体及σ受体显像

近年研究发现 ,σ受体是一类非阿片、非多巴胺受体 ,其结构、生理与生化功能和药理学作用尚不十分清楚。许多肿瘤如恶性黑色素瘤、乳癌、前列腺癌、非小细胞肺癌、结肠癌、肾癌以及来自神经组织的肿瘤均含有高密度的 σ受体。因此 ,研制具有高亲和性、高选择性的 σ受体配体已成为分子核医学的热点之一。这不仅可以对 σ受体的生化和生理功能以及药理作用进行研究 ,也可作为 σ受体阳性肿瘤的显像剂甚至治疗剂。     

EPO, red cells, and serum transferrin receptor in continuous and intermittent hypoxia

PURPOSE: Erythropoietic response in 10 healthy nonsmoking volunteers exposed to normobaric hypoxia continuously or intermittently 12 h daily for 7 d was evaluated in a randomized cross-over study. METHODS: An oxygen content of 15.4% corresponding to an altitude of 2500 m was created by adding nitrogen into room air in a flat. Venous blood samples for hemoglobin (Hb), hematocrit (Hct), reticulocytes, serum erythropoietin (S-EPO), red cell 2,3-diphosphoglycerate (2,3-DPG), serum ferritin (S-Ferrit), and serum soluble transferrin receptor (S-TransfR) were drawn at 8:00 a.m. RESULTS: S-EPO was increased from baseline values of 22.9+/-9.6 and 20.5+/-10.1 U x L(-1) to 40.7+/-12.9 (P < 0.05) and 35+/-14.3 U x L(-1) (P < 0.05) after the first night in continuous and intermittent hypoxia, respectively, and remained elevated throughout both exposures. Hb and Hct values did not show any significant changes. Red cell 2,3-DPG rose from baseline a value of 5.0+/-0.8 to 5.9+/-0.7 mmol x L(-1) (P < 0.05) after the first day in continuous hypoxia and from 5.2+/-0.7 mmol x L(-1) to 6.1+/-0.5 mmol x L(-1) on day 3 (P < 0.05) during intermittent hypoxia. The reticulocyte count rose significantly (P < 0.05) after 5 d in both experiments. S-transferrin receptor level rose significantly from 2.2+/-0.4 and 2.1+/-0.5 mg x L(-1) to 2.6+/-0.5 mg x L(-1) and 2.3+/-0.6 mg x L(-1) on day 5 (P < 0.05), to 2.7+/-0.5 mg x L(-1) and 2.5+/-0.6 mg x L(-1) on day 7 (P < 0.05) under continuous and intermittent hypoxia, respectively. CONCLUSIONS: We suggest that intermittent exposure to moderate normobaric hypoxia 12 h daily for 1 wk induces a similar stimulation of erythropoiesis as continuous exposure.     

Chiral dimethylamine flutamide derivatives--modeling, synthesis, androgen receptor affinities and carbon-11 labeling

Most prostate cancers are androgen dependent upon initial diagnosis. On the other hand, some very aggressive forms of prostate cancer were shown to have lost the expression of the androgen receptor (AR). Although the AR is routinely targeted in endocrine treatment, the clinical outcome remains suboptimal. Therefore, it is crucial to demonstrate the presence and activity of the AR in each case of prostate cancer, before and after treatment. While noninvasive positron emission tomography (PET) has the potential to determine AR expression of tumor cells in vivo, fully optimized PET imaging agents are not yet available. Based on molecular modeling, three novel derivatives of hydroxyflutamide (Compounds 1-3) were designed and synthesized. They contain an electron-rich group (dimethylamine) located on the methyl moiety, which may confer a better stability to the molecule in vivo. Compounds 1-3 have AR binding that is similar or higher than that of the currently used commercial drugs. An automated carbon-11 radiolabeling route was developed, and the compounds were successfully labeled with a 10-15% decay-corrected radiochemical yield, 99% radiochemical purity and a specific activity of 4Ci/mumol end of bombardment (n=15). These labeled biomarkers may facilitate the future quantitative molecular imaging of AR-positive prostate cancer using PET and may also allow for image-guided treatment of prostate cancer.     

Association of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status with total choline concentration and tumor volume in breast cancer patients: An MRI and in vivo proton MRS study

The association of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) status of breast cancer patients with total choline (tCho) concentration and tumor volume was investigated using in vivo proton magnetic resonance spectroscopy and MRI at 1.5 T. Values for tCho concentration were determined in 120 locally advanced breast cancer patients (stages IIB, IIIA, IIIB, and IIIC), 31 early breast cancer patients (stage IIA), 38 patients with benign lesions, and 37 controls. Significantly higher tCho concentration and lower tumor volume were observed in early breast cancer patients compared to locally advanced breast cancer patients (P < 0.05). tCho concentration and tumor volume did not correlate with age and menstruation. tCho cutoff values were obtained for the differentiation of malignant from benign breast tissues (2.54 mmol/kg); malignant versus normal (1.45 mmol/kg) and benign versus normal tissues (0.82 mmol/kg). Estrogen receptor negative patients showed significantly larger tumor volumes, indicating higher angiogenesis with aggressive tumor behavior. Nontriple negative and triple positive patients had a significantly higher tCho concentration compared to triple negative patients (P < 0.05), indicating complex molecular mechanism of cell proliferation and the molecular heterogeneity of breast lesions. The results indicate the potential use of integration of breast ¹H magnetic resonance spectroscopy in diagnostic workup. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.     

Correlation of breast cancer subtypes,based on estrogen receptor,progesterone receptor,and HER2, with functional imaging parameters from 68Ga-RGD PET/CT and 18F-FDG PET/CT

Purpose

Imaging biomarkers from functional imaging modalities were assessed as potential surrogate markers of disease status. Specifically, in this prospective study, we investigated the relationships between functional imaging parameters and histological prognostic factors and breast cancer subtypes.

Methods

In total, 43 patients with large or locally advanced invasive ductal carcinoma (IDC) were analyzed (47.6?±?7.5 years old). ⁶⁸Ga-Labeled arginine-glycine-aspartic acid (RGD) and ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) were performed. The maximum and average standardized uptake values (SUV_max and SUV_avg) from RGD PET/CT and SUV_max and SUV_avg from FDG PET/CT were the imaging parameters used. For histological prognostic factors, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression was identified using immunohistochemistry (IHC) or fluorescent in situ hybridization (FISH). Four breast cancer subtypes, based on ER/PR and HER2 expression (ER/PR+,Her2?, ER/PR+,Her2+, ER/PR?,Her2+, and ER/PR?,Her2?), were considered.

Results

Quantitative FDG PET parameters were significantly higher in the ER-negative group (15.88?±?8.73 vs 10.48?±?6.01, p?=?0.02 for SUV_max; 9.40?±?5.19 vs 5.92?±?4.09, p?=?0.02 for SUV_avg) and the PR-negative group (8.37?±?4.94 vs 4.79?±?3.93, p?=?0.03 for SUV_avg). Quantitative RGD PET parameters were significantly higher in the HER2-positive group (2.42?±?0.59 vs 2.90?±?0.75, p?=?0.04 for SUV_max; 1.60?±?0.38 vs 1.95?±?0.53, p?=?0.04 for SUV_avg) and showed a significant positive correlation with the HER2/CEP17 ratio (r?=?0.38, p?=?0.03 for SUV_max and r?=?0.46, p?<?0.01 for SUV_avg). FDG PET parameters showed significantly higher values in the ER/PR?,Her2? subgroup versus the ER/PR+,Her2? or ER/PR+,Her2+ subgroups, while RGD PET parameters showed significantly lower values in the ER/PR?,Her2? subgroup versus the other subgroups. There was no correlation between FDG and RGD PET parameters in the overall group. Only the ER/PR?,Her2? subgroup showed a significant positive correlation between FDG and RGD PET parameters (r?=?0.59, p?=?0.03 for SUV_max).

Conclusion

⁶⁸Ga-RGD and ¹⁸F-FDG PET/CT are promising functional imaging modalities for predicting biomarkers and molecular phenotypes in breast cancer patients.     

雌激素受体、孕激素受体及原癌基因CerbB-2表达水平与乳腺浸润性导管癌超声乳腺影像报告和数据系统分级的关系

目的探讨雌激素受体(estrogen receptor,ER)、孕激素受体(progesterone receptor,PR)、原癌基因(Cerb B-2)表达水平与乳腺浸润性导管癌(invasive breast cancers,IDC)超声乳腺影像报告和数据系统分级(breast imaging reporting and data system,BI-RADS)的关系。方法对2010年9月~2014年9月医院收治的120例IDC患者行超声检查并进行BI-RADS分级,采用免疫组化法检测患者ER、PR、Cerb B-2阳性表达情况,分析BI-RADS分级与ER、PR、Cerb B-2阳性表达的关系。结果肿块边缘有毛刺征者ER、PR表达阳性率显著高于边缘无毛刺征者(P0.05);肿块内部钙化者Cerb B-2表达阳性率显著高于无钙化者(P0.05);肿块内血流0~Ⅰ级者ER、PR、Cerb B-2表达阳性率显著高于Ⅱ~Ⅲ级者(P0.05);肿块大小、后方回声有无衰减、UE评分与ER、PR、Cerb B-2表达阳性率无明显相关性(P0.05)。ER、PR、Cerb B-2表达阳性的IDC患者BI-RADS分级均显著高于表达阴性者(P0.05)。结论 IDC患者超声征象能够在一定程度上预测ER、PR、Cerb B-2表达的水平,从而为IDC的治疗、预后评估提供参考。     

Immunohistochemical renal expression of aquaporin 2, arginine-vasopressin,vasopressin receptor 2, and renin in saltwater drowning and freshwater drowning

International Journal of Legal Medicine - The diagnosis of drowning is considered one of the most difficult in forensic medicine. Due to the paucity of signs, it is a classical diagnosis by...     

乳腺癌X射线征象与雌激素受体、孕激素受体和C-erbB-2表达相关性的研究进展

乳腺癌是女性最常见的恶性肿瘤之一,其发生、发展过程中大多伴随基因异常表达。雌激素受体（ER）、孕激素受体（PR）及C—erbB-2（即人表皮生长因子受体2）癌基因的表达情况是指导临床内分泌治疗及判断预后的主要参考指标。癌基因表达从不同角度反映了乳腺癌的恶性生物学行为,并引起组织病理学改变,进而形成多种影像学表现。因此,乳腺癌的X射线片表现可在一定程度上反映ER、PR和C-erbB-2的表达情况。乳腺X射线检查因诊断病变的准确率高、操作简单、价格低廉,仍是临床筛查及诊断乳腺癌的首选方法,并成为预测乳腺癌患者ER、PR和c—erbB-2表达情况的无创手段。在无条件做免疫组化的情况下,它对乳腺癌术前评估及非手术治疗发挥了重要作用,具有潜在的临床应用价值。该文主要对乳腺癌影像学表现与ER、PR和CIerbB-2表达的相关性研究进行综述。     

跨膜蛋白受体在LRRC19调节机体先天免疫应答反应中的作用

目的 确定已初步鉴定的富亮氨酸重复结构(LRR)蛋白家族成员LRRC19在脾细胞中的表达及定位,并对其功能进行初步研究.方法 通过生物信息学技术预测LRRC19蛋白结构;mRNA原位杂交和RT-PCR检测LRRC19 mRNA在小鼠脾组织以及不同脾细胞中的表达;以不同细菌刺激LRRC19转染的293T细胞,通过分泌性碱性磷酸酶(SEAP)检测技术观察细胞分泌的NF-κB活性的改变.结果 LRRC19是一种跨膜蛋白,属于LRR蛋白家族成员,胞外区存在串联排列的4个LRR基序,有单一的跨膜结构域,胞内区有2个酪蛋白激酶2(CK2)磷酸化位点;mRNA原位杂交和RT-PCR结果显示,LRRC19 mRNA在脾脏主要表达于B1淋巴细胞;体外实验证实,多种细菌均可使转染LRRC19的细胞NF-κB活性增强.结论 LRRC19可能是一种跨膜受体,可识别不同的病原体保守分子,可能参与介导细胞信号转导,激活NF-κB信号途径,启动靶基因转录,调节先天免疫应答过程.     

EphB-2受体及HER-2与EGFR在结直肠癌中的表达与意义

目的探讨EphB-2受体、HER-2、EGFR的表达与结直肠癌生物学行为的关系。方法采用免疫组化染色检测86例结直肠癌组织标本中EphB-2受体、HER-2、EGFR的表达水平,以结直肠腺瘤组织标本47例作为对照。结果在癌旁无瘤黏膜、结直肠腺瘤和结直肠癌3组中,EphB-2受体的表达阳性率分别为100%（86/86）、95.7%（45/47）和83.7%（72/86）;HER-2表达阳性率分别为34.9%（30/86）、42.6%%（20/47）和74.4%（64/86）;EGFR表达阳性率分别为39.5%（34/86）、46.8%（22/47）和65.1%（56/86）,癌旁无瘤黏膜、结直肠腺瘤与结直肠癌阳性率比较差异具有统计学意义（P〈0.05）。在结直肠癌中EphB-2受体的表达与结直肠癌的分化程度、浸润深度、淋巴结转移有关,而HER-2、EGFR的表达与结直肠癌的浸润深度、淋巴结转移有关。结论 EphB-2受体、HER-2、EGFR对结直肠癌生物学行为有明显影响,可作为临床判断结直肠癌的生物学行为及预后的重要参考指标。     

Effect of peroxisome proliferator-activated receptor gamma agonist, rosiglitazone, on dedifferentiated thyroid cancers

BACKGROUND AND METHOD: As genetic alterations in the gene for the peroxisome proliferator-activated receptor gamma (PPARgamma) have been described and PPAR agonists have been shown to redifferentiate thyroid cancers in animal models, we performed a pilot study in five patients with thyroglobulin-positive and I scan-negative thyroid cancers using the PPARgamma agonist rosiglitazone. RESULTS: Although thyroglobulin levels increased in four of the five patients after 3 months of treatment with rosiglitazone, the I scan remained negative in four patients and became only faintly positive in one patient for two lung metastases that could be correlated with metabolically active lung metastases shown by F-fluorodeoxyglucose positron emission tomography (F-FDG PET) and by computed tomography (CT). F-FDG PET, performed in four patients, revealed metastases of significant size in two patients, including the patient mentioned above and in a second patient confirmed by surgery. CONCLUSIONS: Treatment with rosiglitazone increased the production of thyroglobulin in some patients with thyroid cancers, but only rarely restored scintigraphically significant iodine trapping. It remains to be shown whether longer treatment periods might result in a more efficient redifferentiating effect.     

小鼠烧伤早期巨噬细胞糖皮质激素受体及细胞因子蛋白表达的变化

目的　探讨小鼠烧伤后早期巨噬细胞糖皮质激素受体 (GR)、核转录因子 (NF kB)、肿瘤坏死因子 α(TNF α)和白介素 1β(IL 1β)蛋白表达的变化。 方法　将培养的巨噬细胞株ANA 1注入小鼠腹腔内 ,小鼠行 15 %TBSAⅢ度烧伤 ,收集腹腔巨噬细胞 ,应用免疫组化和Westernblot方法 ,观察烧伤后 2、6小时巨噬细胞GR、NF kB、TNF α和IL 1β蛋白表达的变化。 结果　烧伤后巨噬细胞免疫组化染色GR、NF kB阳性表达减弱 ,TNF α和IL 1β阳性反应增强。Westernblot分析表明烧伤后GR、NF kB蛋白含量降低。 结论　烧伤后巨噬细胞GR、NF kB蛋白减少 ,TNF α和IL 1β增加 ,说明巨噬细胞激活在烧伤后炎症反应中发挥重要作用     

Interpreting enzyme and receptor kinetics: keeping it simple, but not too simple

The hyperbolic parabola is commonly used to summarize kinetics for enzyme reactions and receptor binding kinetics. Depending on the experimental conditions, certain assumptions are valid but others might be violated so that the parameters used to fit this hyperbolic function, the maximum asymptote and the equilibrium constant, require different interpretations. The first topic of this review compares enzyme-induced transformations and receptor binding in terms of the appropriate assumptions. The second topic considers the complication of adding a competitive inhibitor as an enzyme substrate or a receptor ligand and the subtleties of inferring the equilibrium dissociation constant from the concentration of inhibitor (for example unlabeled drug) that leads to the midpoint, IC_50, of an inhibition curve. Receptor binding may be measured directly by a concentration assay or as a pharmacodynamic response variable.     

乳腺癌腋窝淋巴结转移与癌组织雌激素受体、黄体酮受体、Her-2表达的相关性分析

目的 研究不同年龄乳腺癌患者腋窝淋巴结转移率与雌激素受体(ER)、黄体酮受体(PR)和Her-2 表达的关系.方法 回顾性分析259 例乳腺癌的临床病理资料,按年龄分成老年组(>60岁)、中年组(36～60岁)和青年组(≤35岁), 采用χ2检验分析不同年龄组腋窝淋巴结转移率、ER、PR和Her-2 表达率的差异.结果 青年组乳腺癌腋窝淋巴结转移率虽高于中、老年组,但差异无统计学意义(P>0.05).青年组 ER表达率低于中、老年组(P<0.05).青年组PR 阳性率低于中、老年组,但各组之间差异无统计学意义(P>0.05).青年组Her-2阳性率高于中年组(P<0.05).结论 青年乳腺癌的高腋窝淋巴结转移率与ER低表达和Her-2高表达同时出现,提示前者可能与后二者相关联.     

Cardiac beta-adrenergic receptor density measured in vivo using PET, CGP 12177, and a new graphical method.

The in vivo quantification of myocardial beta-adrenergic receptor has been obtained in five closed-chest dogs using positron emission tomography (PET). The ligand was racemic (+/-)[11C] CGP 12177, a very potent hydrophilic antagonist of the beta-adrenergic receptor. A kinetic method appeared unsuitable because of the presence of metabolites which made the input function difficult to measure and also inaccurate. Therefore, a graphical method, based on a particular protocol, was proposed. The animals were injected with a trace amount of (+/-)[11C]CGP 12177, which was followed 40 min later by a second injection of radioligand with a low-specific activity. An additional injection of an excess of unlabeled CGP 12177 was administered after 90 min and allowed for the estimation of the dissociation rate constant. The main advantage of this graphical approach is that the results are obtained without having to measure the input function and therefore without estimating the metabolites. The average value of Bmax was 31 +/- 4 pmole/ml of tissue and the dissociation constant was 0.014 +/- 0.002 min-1.     

DOTA-NOC,a high-affinity ligand of somatostatin receptor subtypes 2, 3 and 5 for labelling with various radiometals

Earlier studies have shown that modification of the octapeptide octreotide in positions 3 and 8 may result in compounds with increased somatostatin receptor affinity that, if radiolabelled, display improved uptake in somatostatin receptor-positive tumours. The aim of a recent research study in our laboratory was to employ the parallel peptide synthesis approach by further exchanging the amino acid in position 3 of octreotide and coupling the macrocyclic chelator DOTA(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) to these peptides for labelling with radiometals like gallium-67 or -68, indium-111, yttrium-90 and lutetium-177. The purpose was to find radiopeptides with an improved somatostatin receptor binding profile in order to extend the spectrum of targeted tumours. A first peptide, [¹¹¹In,⁹⁰Y-DOTA]-1-Nal³-octreotide (¹¹¹In,⁹⁰Y-DOTA-NOC), was isolated which showed an improved profile. In^III-DOTA-NOC exhibited the following IC₅₀ values (nM) when studied in competition with [¹²⁵I][Leu⁸, d-Trp²², Tyr²⁵]somatostatin-28 (values for Y^III-DOTA-NOC are shown in parentheses): sstr2, 2.9±0.1 (3.3±0.2); sstr3, 8±2 (26±1.9); sstr5, 11.2±3.5 (10.4±1.6). Affinity towards sstr1 and 4 was very low or absent. In^III-DOTA-NOC is superior to all somatostatin-based radiopeptides having this particular type of binding profile, including DOTA-lanreotide, and has three to four times higher binding affinity to sstr2 than In^III,Y^III-DOTA-Tyr³-octreotide (In^III,Y^III-DOTA-TOC). In addition, [¹¹¹In]DOTA-NOC showed a specific and high rate of internalization into AR4-2J rat pancreatic tumour cells which, after 4 h, was about two times higher than that of [¹¹¹In]DOTA-TOC and three times higher than that of [¹¹¹In]DOTA-octreotide ([¹¹¹In]DOTA-OC). The internalized radiopeptides were externalized intact upon 2 h of internalization followed by an acid wash. After 2–3 h of externalization a plateau is reached, indicating a steady-state situation explained by reactivation of the receptors followed by re-endocytosis. Biodistribution studies in CA 20948 tumour-bearing rats showed rapid clearance from all sstr-negative tissues except the kidneys. At 4 h the uptake of [¹¹¹In]DOTA-NOC in the tumour and sstr-positive tissues, such as adrenals, stomach and pancreas, was three to four times higher than that of [¹¹¹In]DOTA-TOC. Differential blocking studies indicate that this is at least partially due to the uptake mediated by sstr3 and sstr5. These very promising preclinical data justify the use of this new radiopeptide for imaging and potentially internal radiotherapy studies in patients.Abbreviations of the common amino acids are in accordance with the recommendations of IUPAC-IUB [IUPAC-IUB Commission of Biochemical Nomenclature (CBN), Symbols for amino-acid derivatives and peptides, recommendations 1971. Eur J Biochem 1972; 27:201–207].