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61.
Anastasia Nikolopoulou Theodosia Maina Petros Sotiriou Paul Cordopatis Berthold A. Nock 《Journal of peptide science》2006,12(2):124-131
Two somatostatin analogues, [99mTc]Demotide and [99mTc]Demotate 4, were compared with [99mTc]Demotate 1, a previously reported somatostatin receptor subtype 2 (sst2) targeting tracer. Conjugates were prepared by coupling an open‐chain tetraamine chelator to D ‐Phe1 of [Tyr3]‐octreotide or [Tyr3]‐octreotate, respectively, via a p‐benzylaminodiglycolic acid spacer adopting solid‐phase peptide synthesis techniques. Peptide conjugates were collected in a highly pure form after chromatographic purification. Eventually, [99mTc]Demotide and [99mTc]Demotate 4 were obtained in ~1 Ci/µmol specific activity and >96% purity after labeling under alkaline conditions. Demotide and Demotate 4 exhibited similar high binding affinities for the sst2 expressed in AR4‐2J cells with IC50 values 0.16 and 0.10 nM, respectively. The (radio)metallated analogues [99mTc]Demotide and [99mTc]Demotate 4 showed equally high affinities to the sst2 during saturation binding assays in AR4‐2J cell membranes (Kds 0.08 and 0.07 nM, respectively). During incubation at 37 °C with AR4‐2J cells, the radiopeptides internalized effectively via a receptor‐mediated process, with [99mTc]Demotate 4 exhibiting a faster internalization rate than [99mTc]Demotide. After injection in athymic mice bearing sst2‐expressing AR4‐2J tumors, the radiotracers showed high and specific uptake in the tumor (>25%ID/g at 1 h) and in the sst2–positive organs. However, both [99mTc]Demotide and [99mTc]Demotate 4 showed unfavorably higher background activity, especially in the abdomen, in comparison to [99mTc]Demotate 1 and are, therefore, less suited than [99mTc]Demotate 1 for sst2‐targeted tumor imaging in man. Copyright © 2005 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
62.
Junji Sagara Tadafumi S. Tochikura Hajime Tanaka Yoshihiro Baba Shoichiro Tsukita Sachiko Tsukita Akihiko Kawai 《Microbiology and immunology》1998,42(4):289-297
In our monoclonal antibody (MAb) stocks prepared against the BHK-21 cell antigens, two (#11875 and 28276) recognized a 21-kDa polypeptide (referred to as VAP21) which is efficiently incorporated into the rabies virion. By using these MAbs, we isolated the cDNA clones that encoded a polypeptide of 144 amino acids from our BHK-21 cell cDNA library. Based on the following evidence, the cDNA was assumed to encode a full-length sequence of VAP21 antigen: i) expression of the cDNA in animal cells resulted in the production of a polypeptide recognized by the two MAbs, and its electrophoretic mobility was the same as that of authentic VAP21 antigen; and ii) immunization with the products from the cDNA-transformed E. coli cells raised specific antibodies in rabbits that recognized a 21-kDa polypeptide in the virion. From the deduced amino acid sequence, it is suggested that the VAP21 antigen has a molecular structure of type-I transmembrane protein containing characteristic proline-rich and glycine-rich regions in its ectodomain. Homology searches resulted in finding homologous sequences (totally about 40% homology) in the human MIC2 gene product (CD99; 32-kDa) of T lymphocytes. These results suggest that the VAP21 antigen in the rabies virion is a cellular CD99-related transmembrane protein. 相似文献
63.
目的:通过放射性核素~(99m)Tc标记BmK CT多肽制备靶向胶质瘤的显像剂,探讨~(99m)?Tc-BmK CT用于胶质瘤显像的可行性。方法:采用BmK CT多肽游离的氨基与DTPA酸酐反应得到BmK CT-DTPA,经99m Tc标记后通过柱层析分离纯化制备~(99m)?Tc-BmK CT。测定标记物在PBS溶液和血清中不同时间点放射性化学纯度,评价BmK CT-~(99m)?Tc体外稳定性。新西兰白兔耳缘静脉注射~(99m)Tc-BmK CT进行SPECT显像,观察不同时间点体内的放射性分布。皮下胶质瘤裸鼠经尾静脉注射~(99m)Tc-BmK CT,观察不同时间点肿瘤的摄取情况;注射后4 h处死裸鼠,分离肿瘤和主要器官进行离体SPECT显像,并用勾画感兴趣区法分析相对放射性计数。结果:~(99m)Tc标记BmK CT多肽标记率大于80%,经柱层析分离纯化后放射性化学纯度大于99%。标记物在PBS和血清稳定性良好,6 h内放射性化学纯度均大于95%,12 h内放射性化学纯度大于90%。正常白兔SPECT显像表明~(99m)Tc-BmK CT主要浓聚在肝脏、脾脏和肾脏,软组织持续显影微弱,甲状腺区及胃肠未见核素浓聚;显像剂主要通过泌尿系统排泄,24 h肾脏与肝脏显影接近。胶质瘤裸鼠SPECT显像表明,注射后4 h肿瘤显像清楚,ROI分析结果显示肿瘤/肌肉比4.26±0.25,标记物在肿瘤内代谢缓慢,8 h肿瘤部位仍有较高摄取。结论:本研究成功制备了~(99m)Tc标记BmK CT多肽,标记物主要被肝、脾和肾摄取,经泌尿系统排泄;~(99m)Tc-BmK CT能够在皮下胶质瘤中浓聚,注射后4 h肿瘤显影清晰,瘤内代谢缓慢,有潜力成为一种新型胶质瘤分子探针。 相似文献
64.
双抗双高夏大豆种质鲁99-2的选育 总被引:3,自引:2,他引:1
优良种质创新是大豆新品种选育的关键。经过近20年的中间种质创新、亲本筛选、抗性选育、鉴定和品质检验等研究,育成了双抗双高的夏大豆优良种质鲁99-2。其对大豆胞囊线虫1、3、5号生理小种的抗性均为1级;对大豆花叶病毒y6株系的抗性也为1级;籽粒脂肪含量平均为22.09%,高值为22.67%;蛋白质含量平均为43.29%,高值为45.0%;蛋白质和脂肪合计含量平均为65.38%,高值达66.40%。鲁99-2的育成说明创造和利用优良种质、选择适宜的杂交亲本和采用有效的选育方法等对大豆育种至关重要。 相似文献
65.
M. Bashir-Uddin Surfraz Stephen J. Mather Philip J. Blower 《Journal of inorganic biochemistry》2009,103(7):971-977
Electrospray mass spectrometry (ESMS) of certain peptides labelled with 99mTc via hydrazinonicotinamide (HYNIC) with tricine as co-ligand shows one Tc-bound tricine, whereas typically two are observed. We speculated that this was due to coordination of a neighbouring histidine (His) or glutamate (Glu). To investigate this possibility, several short peptides incorporating lysine (HYNIC), with and without His and Glu at different positions in the sequence, were radiolabelled with 99mTc, using tricine, ethylenediaminediacetic acid (EDDA) and nicotinic acid as co-ligands. The products were examined by HPLC-ESMS, cysteine challenge and bovine serum albumin (BSA) challenge. Peptides with His nearby on either side of lysine (HYNIC) contained only one tricine and showed markedly enhanced structural homogeneity and stability to cysteine challenge and BSA binding, except those with His located at the N-terminus. Peptides without His, or with neighbouring N-terminal His, contained two tricines and were less stable to cysteine challenge and BSA binding. Glu participated in Tc-binding but did not enhance stability. We conclude that neighbouring His or Glu side chains coordinate to Tc and this could alter peptide or protein conformation. Inclusion of His in a neighbouring position to lysine (HYNIC) enhances stability, improves homogeneity and reduces the demand of the metal center for binding to additional co-ligands. 相似文献
66.
Yanhong Sun Yunfeng Ren Hua Zhu Yuanqing Zhang Guifeng Liu Chunchun Zhang Liliang Huang Jia Xu Yujin Qi Yu-Mei Shen 《Journal of biological inorganic chemistry》2009,14(6):899-904
β-Elemene, (5S,7R,10S)-(−)-(1-methyl-1-vinyl-2,4-diisopropenylcyclohexane), is an anticancer agent from traditional Chinese herbal medicine. Three
novel 99mTc(CO)3–β-elemene conjugates were synthesized successfully, and compared with β-elemene exhibited improved water solubility. A biodistribution
and micro single photon emission computed tomography image study showed there is a visible accumulation in Lewis lung cancer
tumors.
Y. Sun and Y. Ren contributed equally to this paper. 相似文献
67.
Julie Cattelotte Nicolas Tournier Nathalie Rizzo-Padoin† Alfred H. Schinkel‡ Jean-Michel Scherrmann Salvatore Cisternino§ 《Journal of neurochemistry》2009,108(3):767-775
Cationic 99m Tc-agents like 99m Tc-hexakis-2-methoxyisobutyl isonitrile (99m Tc-MIBI) cannot be used for brain imaging because they do not enter the brain as readily as some uncharged 99m Tc-compounds. The mechanism by which cationic 99m Tc-agents are transported across the blood–brain barrier (BBB) remains unclear. We explored 99m Tc-MIBI transport by in situ mouse brain perfusion to determine the influence of BBB features like the ATP-binding cassette transporters (Abcb1/P-glycoprotein (P-gp), Abcc1/Mrp1, and Abcg2/Bcrp), organic cation transporters (Slc22a1-3/Oct1-3), the transmembrane potential and the dipole membrane potential. P-gp reduced 99m Tc-MIBI transport across the BBB of P-gp-deficient mice 2.2-fold, as confirmed by PSC833 and GF120918 inhibition. Paradoxically verapamil decreased its transport '0.6-fold'. Reducing the BBB dipole membrane potential with tetraphenylborate or phloretin increased 99m Tc-MIBI transport about 12- and 20-fold, respectively. Guanidine, diphenhydramine, and carnitine significantly decreased 99m Tc-MIBI transport, but tetraethylammonium did not. 99m Tc-MIBI transport at the BBB is restricted by P-gp but not by Mrp1 or Bcrp. Some organic cations reduced the influx of 99m Tc-MIBI into the brain independently of Oct1, 2 and 3, but this could be due to their effect on another cation transporter. The membrane dipole potential of the luminal BBB membrane appeared to be the main factor restricting 99m Tc-MIBI permeability. 相似文献
68.
Himanshu Gupta M. Aqil R. K. Khar Asgar Ali Aseem Bhatnagar Gaurav Mittal Sanyog Jain 《AAPS PharmSciTech》2009,10(2):540-546
In situ gel-forming systems have drawn much attention of current researchers to overcome the poor bioavailability from the conventional
eye drops. The present work described formulation and pharmacoscintigraphic evaluation of timolol-maleate-loaded chitosan/hydroxy
propyl methyl cellulose (HPMC)-based polymer matrix for enhanced ocular retention. Chitosan and HPMC ratio was optimized and
formulation was characterized for various in vitro parameters. The ocular retention was studied on New Zealand rabbits by gamma scintigraphy, which is a very simple and noninvasive
technique. For scintigraphy study, the drug timolol maleate was radiolabeled 99mTc by direct labeling method using SnCl2·2H2O as reducing agent. The labeling procedure was optimized to get maximum labeling efficiency (>98%). In vitro stability of the radiolabeled drug (99mTc-timolol maleate complex) was checked and it was found to be stable for up to 24 h. Plain drug eliminates rapidly as significant
activity was recorded in kidney and bladder after 2 h of ocular administration. It was evident from the scintigraphic images
and the time–activity curve plotted from the data that the plain drug solution cleared very rapidly from the corneal region
and reached into systemic circulation via nasolachrymal drainage system, as significant activity was recorded in kidney and
bladder after 2 h of ocular administration. Developed formulation cleared at a slow rate and remained at corneal surface for
longer time duration. No radioactivity was observed in systemic circulation after 2 h. Ocular irritation of the developed
formulation was also checked by hen’s egg chorioallantoic membrane test and formulation was found to be practically nonirritant.
The study signified the potential of gamma scintigraphy in evaluation of novel drug delivery systems in a noninvasive manner. 相似文献
69.
利用噬菌体展示技术已选出了多条与靶结合的肽. 然而,即使是体内直接筛选得到的,肽与肿瘤或靶器官的体内结合并不理想. 为了更好地理解噬菌体在体内的循环, 通过MAG3 99mTc标记噬菌体肽库,研究了肽库在体内分布. 体内分布实验结果显示,99mTc-噬菌体主要分布在肝和脾中,而心脏、肌肉、脑和胰腺这些器官或组织中的分布非常低. 99mTc-噬菌体在胃、肠和骨中的累积,随着时间延长在不断升高,其他器官中的吸收则在不断降低. 从5 min到30 min,99mTc-噬菌体在血中清除迅速. 当噬菌体在体内循环足够长的时间后,一些噬菌体颗粒可以穿透血管进入并内化在器官或组织中. 总之,为了筛选具有高特异性和亲和性的肽,应该根据靶器官和筛选部位的不同,在筛选前确定合适的噬菌体在体内的循环时间. 相似文献
70.
OBJECTIVE: The aim of this study was to investigate the role of HLA-DR, HLA-G and CD99 during cervical carcinogenesis and to examine the prognostic significance of these protein expressions in invasive squamous cell carcinoma (SCC). METHODS: Using specific antibodies for HLA-DR, HLA-G and CD99, we examined protein expressions in 19 normal cervix, 15 mild dysplasia (CIN I), 22 moderate dysplasia (CIN II), 23 severe dysplasia (CIN III), and 34 invasive squamous cell carcinoma by immunohistochemistry. And we detected the expression of Ki67 in the same specimens. RESULTS: None of normal cervix and CINs except three cases of CIN III expressed HLA-DR. HLA-DR expression increased progressively with the grade of the tumor, and significant differences could be observed between grade 1 and grade 2 (P<0.01) and between grade 1 and grade 3 (P<0.05). In all normal epithelial control samples, HLA-G expression was seen in ectocervical squamous and endocervical columnar epithelium and the staining was strong and uniform. Only a small proportion of CINs and SCCs showed reduced expression of HLA-G. Compared with the results in the control samples, CINs and SCCs showed significantly reduced expression of HLA-G (P<0.001). SCCs showed significantly increased expression of CD99 when compared with normal cervix and CINs (P<0.05). Ki67 was expressed in all specimens. Significant differences were observed between CINs and normal cervix (P<0.001) and SCCs and controls (P<0.001), but no significant differences could be observed between SCCs and CINs. None of the expressions of these proteins was associated with any of clinicopathological parameters. CONCLUSIONS: These results indicate that increased expression of HLA-DR and CD99 may be related to the evolution of cervical cancer. All protein expressions were not associated with clinicopathological parameters. 相似文献