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AbstractAbstract
[en] The rat posterodorsal medial amygdala (MePD) links emotionally charged sensory stimuli to social behavior, and is part of the supramedullary control of the cardiovascular system. We studied the effects of microinjections of neuroactive peptides markedly found in the MePD, namely oxytocin (OT, 10 ng and 25 pg; n=6/group), somatostatin (SST, 1 and 0.05 μM; n=8 and 5, respectively), and angiotensin II (Ang II, 50 pmol and 50 fmol; n=7/group), on basal cardiovascular activity and on baroreflex- and chemoreflex-mediated responses in awake adult male rats. Power spectral and symbolic analyses were applied to pulse interval and systolic arterial pressure series to identify centrally mediated sympathetic/parasympathetic components in the heart rate variability (HRV) and arterial pressure variability (APV). No microinjected substance affected basal parameters. On the other hand, compared with the control data (saline, 0.3 µL; n=7), OT (10 ng) decreased mean AP (MAP_5_0) after baroreflex stimulation and increased both the mean AP response after chemoreflex activation and the high-frequency component of the HRV. OT (25 pg) increased overall HRV but did not affect any parameter of the symbolic analysis. SST (1 μM) decreased MAP_5_0, and SST (0.05 μM) enhanced the sympathovagal cardiac index. Both doses of SST increased HRV and its low-frequency component. Ang II (50 pmol) increased HRV and reduced the two unlike variations pattern of the symbolic analysis (P<0.05 in all cases). These results demonstrate neuropeptidergic actions in the MePD for both the increase in the range of the cardiovascular reflex responses and the involvement of the central sympathetic and parasympathetic systems on HRV and APV
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Available from http://dx.doi.org/10.1590/1414-431X20144095; Available from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4321218; PMCID: PMC4321218; PMID: 25424367; OAI: oai:pubmedcentral.nih.gov:4321218; This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.; Country of input: International Atomic Energy Agency (IAEA)
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Journal Article
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Brazilian Journal of Medical and Biological Research; ISSN 0100-879X;
; v. 48(2); p. 128-139

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AbstractAbstract
[en] The high level expression of somatostatin receptors (SSTR) on various tumor cells has provided the molecular basis for successful use of radiolabeled octreotide/lanreotide analogs as tumor tracers in nuclear medicine. The vast majority of human tumors seem to over express the one or the other of five distinct hSSTR subtype receptors. Whereas neuroendocrine tumors frequently over express hSSTR2, intestinal adenocarcinomas seem to over-express more often hSSTR3 or hSSTR4, or both of these hSSTR. In contrast to 111In-DTPA-DPhe1-octreotide (OCTREOSCAN(R)) which binds to hSSTR2 and 5 with high affinity (Kd 10-100 nM) and does not bind to hSSTR1 and hSSTR4, 111In/90Y-DOTA-lanreotide was found to bind to hSSTR2, 3, 4 and 5 with high affinity, and to hSSTR1 with lower affinity (Kd 200 nM). Based on its unique hSSTR binding profile, 111-DOTA-lanreotide was suggested to be a potential radioligand for tumor diagnosis, and 90Y-DOTA-lanreotide suitable for receptor-mediated radionuclide therapy. As opposed to 111In-DTPA-DPhe1-octreotide and 111In-DOTA-DPhe1-Tyr3-octreotide, discrepancies in the scintigraphic results were seen in about one third of (neuroendocrine) tumor patients concerning both the tumor uptake as well as detection of tumor lesions. On a molecular level, these discrepancies seem to be based on a higher high-affinity binding of 111In-DOTA-DPhe1-Tyr3-octreotide to hSSTR2. Other somatostatin analogs with divergent affinity to the five known hSSTR subtype receptors have also found their way into the clinics, including 99mTc-depreotide (NEOSPECT(R); NEOTECT (R)). Most of the imaging results are reported for neuroendocrine tumors (octreotide analogs) or non-small cell lung cancer (99mTc-depreotide), indicating high diagnostic capability of this type of receptor tracers. Consequently to their use as receptor imaging agents, hSSTR recognizing radioligands have also been implemented for experimental receptor-targeted radionuclide therapy. The study MAURITIUS (Multicenter Analysis of a Universal Receptor Imaging and Treatment Initiative, a eUropean Study), a Phase 2a study, showed in patients with a calculated tumor dose >10 Gy/GBq 90Y-DOTA-lanreotide, the proof-of-principle for treating tumor patients with receptor imaging agents. Overall treatment results in >60 patients indicated stable tumor disease in roughly 35% of patients and regressive disease in 15% of tumor patients with different tumor entities. No acute or chronic severe hematological toxicity, change in renal or liver function parameters due to 90Y-DOTA-lanreotide, was reported. 90In-DOTA-DPhe1-Tyr3-octreotide may show a higher tumor uptake in neuroendocrine tumor lesions and may therefore provide even better treatment results in tumor patients, but there is only limited excess to long-term and survival data at present. Besides newer approaches and recent developments of 188Re-labeled radioligands no clinical results on the treatment response is available yet. In conclusion, several radioligands have been implemented on the basis of peptide receptor recognition throughout the last decade. A plenitude of preclinical data and clinical studies confirm proof-of-principle for their use in diagnosis as well as therapy of cancer patients. However, an optimal radio peptide formulation does not yet exist for receptor-targeted radionuclide therapy
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AbstractAbstract
[en] Neuroendocrine tumors (NETs) consist of a heterogeneous group of tumors that are uptake neuroamine and/or specific receptors, such as somatostatin receptors, which can play important roles of the localization and treatment of these tumors. When considering therapy with radionuclides, the best radioligand should be carefully investigated. 131I-MIBG and beta-particle emitter labeled somatostatin analogs are well established radionuclide therapy modalities for NETs. 111In, 90Y and 177Lu radiolabelled somatostatin analogues have been used for treatment of NETs. Further, radionuclide therapy modalities, for example, radioimmunotherapy, radiolabeled peptides such as minigastrin are currently under development and in different phases of clinical investigation. For all radionuclides used for therapy, long-tem and survival statistics are not yet available and only partial tumour responses have been obtained using 131I-MIBG and 111In-octreotide. Experimental results using 90Y-DOTA-lanreotide as well as 90Y-DOTA-D -Phe1-Tyr3-octreotide and/or 177Lu-DOTA-Tyr3-octreotate have indicated the possible clinical potential of radionuclides receptor-targeted radiotherapy. It may be hoped that the efficacy of radionuclide therapy will be improved by co-administration of chemotherapeutic drugs whose antitumoral properties may be synergistic with that of irradiation
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43 refs, 2 figs
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Journal Article
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Nuclear Medicine and Molecular Imaging; ISSN 1975-129X;
; v. 40(2); p. 90-95

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Rogers, B. E.
University of Alabama at Birmingham (United States). Funding organisation: USDOE Office of Energy Research ER (United States)2002
University of Alabama at Birmingham (United States). Funding organisation: USDOE Office of Energy Research ER (United States)2002
AbstractAbstract
[en] The goal of this proposal was to construct and evaluate adenoviral vectors encoding for the human somatostatin receptor subtype 2 (SSTr2) in the context of human prostate cancer
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6 Jun 2002; 5 p; FG--02-01ER63193; Also available from OSTI as DE00836626; PURL: https://www.osti.gov/servlets/purl/836626-gYNtGl/native/
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AbstractAbstract
[en] We successfully achieved complete regression of a pancreatic pseudocyst after Ethibloc embolization of a fistula between the cyst and the pancreatic duct. Previous treatment by percutaneous drainage over 6 weeks had failed. Treatment with a somatostatin analog had not been undertaken
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Copyright (c) 1997 Springer-Verlag New York Inc.; Country of input: International Atomic Energy Agency (IAEA)
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Petrovic, D.; Djokic, D.; Mikoljaczak, R.; Dariusz, P.
4. Berder Meeting - Biology of ionizing radiation - Booklet2013
4. Berder Meeting - Biology of ionizing radiation - Booklet2013
AbstractAbstract
[en] The full text of the publication follows. Because of radiation of high beta-energy and short half-life time, 90Y is widely used for the labelling of targeted molecules that are used in the treatment of cancer. DOTATATE is an analogous of somatostatin, the naturally occurring peptide with diverse functions. The role of DOTATATE is to introduce radioactive particle in solid tumor. The aim of this study was to explore possible competition of iron ions with yttrium ions during the labelling process of DOTATATE. The importance of this research can be seen in the fact that during the process of labelling, syringes with steel needles were used. Series of different concentrations of iron were prepared. The molar ratios of DOTATATE/Fe were: 2:1, 5:1 and 10:1. After that, the standard procedure of labelling DOTATATE with yttrium was performed using 925 MBq of 90Y as 90Y chloride solution. The control of radioactivity was carried out on CAPINTEC CRC 15-BETA dose calibrator that had been previously calibrated for 90Y. The control of radiochemical purity of the radiolabelled peptide was carried out by HPLC, ITLC and by extraction chromatography Sep-Pak columns. Additionally, the concentration of contaminating Fe was confirmed by ICP-optical emission spectrometry. Obtained results showed that iron contamination of the solution significantly reduces the yield during the labelling of DOTATATE with 90Y as ions compete with iron ions in yttrium labelling. (authors)
Primary Subject
Source
Canceropole Grand Ouest, CHU Nantes, 5 allee de l'ile Gloriette, 44093 Nantes (France); 33 p; 2013; p. 22; 4. Berder Meeting - Biology of ionizing radiation; Ile de Berder, Larmor-Baden (France); 22-25 Sep 2010; The full text of the publication is entered in this record and is also available from the INIS Liaison Officer for France, see the 'INIS contacts' section of the INIS website for current contact and E-mail addresses: http://www.iaea.org/INIS/contacts/
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Lengyel, A.M.J.; Nieuwenhuyzen-Kruseman, A.C.; Grossman, A.; Besser, G.M.
Proceedings of the 16. Brazilian Congress of Endocrinology and Metabology1984
Proceedings of the 16. Brazilian Congress of Endocrinology and Metabology1984
AbstractAbstract
No abstract available
Original Title
Efeitos da glicose na secrecao hipotalamica de somatostatina-14 (S-14) e de somatostatina-28 (S-28) 'in vitro'
Primary Subject
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Comissao Organizadora do 16. Congresso Brasileiro de Endocrinologia e Metabologia; 236 p; 1984; p. 123; 16. Brazilian Congress of Endocrinology and Metabology; Canela, RS (Brazil); 27-31 Oct 1984; Published in summary form only.
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AbstractAbstract
[en] Full text of publication follows. In the development of targeted imaging and therapy agents the most important challenge and prerequisite is to identify and validate the molecular targets of any disease. The targets should be specific, relevant, easily accessible and highly expressed. In addition they should have no or at least very low expression in normal tissue. Among the many drug targets is the large family of G-protein coupled receptors (GPCRs). It is the most important family of marketed drugs and the basic accomplishments in the field were recognised by the award of the recent Nobel price in chemistry. GPCRs also play a role in cancer. Several of these receptors are massively over-expressed in different human tumors such as neuroendocrine tumors (over-expression of the somatostatin receptor family), prostate and breast tumors (bombesin receptor family), brain tumors (NK1 receptor) etc.. This allows to develop (nuclear, MRI, optical) probes for imaging and potentially targeted therapy (theragnostics). Natural ligands targeting GPCRs are often peptides. They need to be modified for metabolic stability, modified for labeling with radio-metals (conjugation of bifunctional chelators) or radio-halogens (prosthetic groups). Preserved biological integrity after modification and labeling needs to be assured, long retention times in the tumor is important, conferred by internalisation. Radio-metal labeling in particular needs to be reasonably fast and the radio metal complexes have to show high stability with regard to radio-metal release. These prerequisites will be discussed for somatostatin receptor based radio-peptides in particular. For a successful clinical application preclinical imaging and biodistribution in adequate animal models are mandatory. New tracers for positron emission tomography (PET) and single photon emission computed tomography (SPECT) will be presented for neuroendocrine tumors and prostate cancer. In particular radiolabeled antagonists will be discussed. They appear to have better imaging properties than agonists. How (coordination) chemistry affects pharmacology will be an important focus of this lecture. Another important aspect will be to discuss the different properties of agonistic radioligands which cause signaling and internalisation (transfer of the receptor ligand complex into the cell) and antagonists which block the action of agonists and are not internalised but may recognise more receptor binding sites. Finally early and extended human use studies will be presented for the 2 tumor entities mentioned above. It will be demonstrated how improved peptide and chelate chemistry improves diagnostic accuracy and therapeutic outcome in tumor treatment. (author)
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Laboratoire Subatech, 4 rue Alfred Kastler, 44307 Nantes (France); 171 p; 2015; p. 61; WIPR 2013: Radiopharmaceuticals - from research to industry; Nantes (France); 9-12 Jul 2013; Available in abstract form only, full text entered in this record
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Canessa, J.; Arteaga, P.; Cerda, G.; Ilzauspe, J.; Massardo, T.; Pineda, P.; Gil, M. Cecilia, E-mail: josecanessa@gmail.com
International Conference on Advances in Radiation Oncology (ICARO). Book of extended synopses2009
International Conference on Advances in Radiation Oncology (ICARO). Book of extended synopses2009
AbstractAbstract
No abstract available
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Source
International Atomic Energy Agency, Division of Human Health, Vienna (Austria); American Association of Physicists in Medicine (AAPM), One Physics Ellipse, College Park, MD (United States); American Brachytherapy Society (ABS), Reston, VA (United States); American Society for Radiation Oncology (ASTRO), Fairfax, VA (United States); European Society for Therapeutic Radiology and Oncology (ESTRO), Brussels (Belgium); International Association for Radiation Research (IARR), Radiation Biology Center, Kyoto University, Sakyo-ku (Japan); International Commission on Radiation Units and Measurements, Inc. (ICRU), Bethesda, MD (United States); Asia-Oceania Federation of Organizations for Medical Physics (AFOMP), Osaka University, Suita-city (Japan); Asociacion Latinoamericana de Terapia Radiante Oncologica (ALATRO), Cancun (Mexico); European Association of Nuclear Medicine (EANM), Vienna (Austria); European Federation of Organisations for Medical Physics (EFOMP), Udine (Italy); International Network for Cancer Treatment Research (INCTR), Brussels (Belgium); International Organization for Medical Physics (IOMP), Kogarah, NSW (Australia); Trans Tasman Radiation Oncology Group (TROG), Department of Radiation Oncology, Calvary Mater Newcastle, NSW (Australia); International Union Against Cancer (UICC), Geneva (Switzerland); 353 p; 2009; p. 171-172; ICARO: International Conference on Advances in Radiation Oncology; Vienna (Austria); 27-29 Apr 2009; IAEA-CN--170/145P; No abstract provided; 6 refs
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AbstractAbstract
[en] The technique described is for labeling of another somatostatin analog based on Tyr3-octreotide, using hydrazinonicotinico acid (HYNIC) as a ligand for technetium and EDDA has been successful in preclinical trials and subsequently has developed a formulation for the preparation of kits lyophilized
[es]
La tecnica descrita para la marcacion de otro analogo de somatostatina basado en Tyr3-Octreotide, empleando acido hidrazinonicotinico (HYNIC) como ligando para el tecnecio y EDDA como coligando ha obtenido buenos resultados en ensayos preclinicos y posteriormente fue desarrollada una formulacion para la preparacion de kits liofilizados. DISENO: descripcion de un estudio de investigacion basica de produccion de farmacos. INTER VENCIONES: el peptido de HYNIC-D- Phe3-Tyr3-Octreotide fue sintetizado por el piChem (Graz, Austria), con una pureza quimica > 98%. El pertecnectato 99mTcO4- se ha obtenido del generador ELumatic 99Mo/99mTc de CIS-BIO; los otros reactivos fueron calidad Aldrich-Sigma. El procedimiento se realizo en condiciones asepticas y normas GMP . Se prepararon: EDDA en agua destilada 20mg/ml, el cual se calento por 10 minutos en bano Maria hasta su completa dilucion. Tricina y manitol en agua destilada a una concentracion de 40mg/mL y 100mg/mL respectivamente. Esta solucion se purgo con N2 gaseoso por 15 minutos y se mezclo con la solucion EDDA. Luego se disolvio el HYNIC-TOC en Etanol al 10% a una concentracion final de 0.5?g/?L y SnCl2 en HCl 0.1N (purgado previamente con N2) en una concentracion de 1mg/mL, Esta mezcla se adiciono a la mezcla de EDDA mas tricina y manitol. Mediante un filtro de 0.22 micras y baja union a proteina se dispenso 1 mL de la mezcla anterior en un vial de vidrio para obtener una concentracion final de 20?g de HYNIC-TOC, EDDA 10mg, Tricina 20mg y Manitol 50mg. Se congelo a - 47 grados para posteriormente realizar un ciclo de liofilizacion (liofilizador L YPH-LOCK 18 LABCONCO) durante 24 h. Fueron adicionados, 1.5mL de Na2HPO4 0.2M para reconstitutir el vial de EDDA/HYNIC-TOC y 99mTc de 25-30mCi (0.8-1GBq) en 2 mL de SSN 0.9%; posteriormente se incubo el vial en bano de agua a ebullicion (+/- 92 o C) por 20 min. La disolucion fue rapida, completa y libre de particulas. El pH fue de 6-7 verificado con papel de pH. La pureza radioquimica fue determinada por cromatografia en capa delgada utilizando ITLC-SG y tres solventes: metil-etil-cetona para determinar tecnecio libre (Rf=1), PBS para determinar 99mTc-coligando (Rf=1) y acetonitrilo-agua (1:1) para determinar 99mTc-coloide (Rf=0). Se realizo una prueba de union a proteinas plasmaticas incubando 50uL del peptido marcado (500 uCi y 1 ug del peptido) con 450uL de suero a 37oC durante 15 minutos. Para el control negativo, se mezclaron 50uL del peptido marcado con 450uL de SSN 0.9% y se incubaron bajo las mismas condiciones. Despues de la incubacion, se tomaron 25uL del peptido y se colocaron en una columna de MicrospinR G50 la cual fue centrifugada. Al eluido recogido y a la columna se les midio la actividad en un contador de NaI y se calculo el porcentaje de peptido unido a proteina como el porcentaje del eluido en la columna. Este procedimiento se repitio a los 30 minutos, 1, 2 y 4 horas. Para determinar la estabilidad del plasma se tomaron 25 uL del peptido incubado durante 4 horas y se mezclaron con 25 uL acetonitrilo y se centrifugo a 2000 RPM por 2 min. El eluido se analizo con ITLC en las mismas condiciones descritas para la pureza radioquimica. Las pruebas de esterilidad y apirogenicidad de los kits fueron realizadas por procedimientos farmaceuticos convencionales. CONCLUSIONES: Se han fabricado 3 lotes de 6 viales cada uno; a dos de los 6 viales (de cada lote) se les han realizado los controles de calidad indicados con resultados de calidad optimos. (author)Original Title
Fabricacion de un kit EDDA/Hynic-Tyr3-Octeotride liofilizado para marcacion con 99mTc en el Instituto Nacional de Cancerologia
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11. Congress of Colombian Society of Nuclear Medicine; Bogota (Colombia); 2-4 Nov 2007; Available on-line: http://www.wjnm.org/showBackIssue.asp?issn=1450-1147; year=2008; volume=7; issue=3; month=July-September
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World Journal of Nuclear Medicine; ISSN 1450-1147;
; v. 7(3); p. 196-197

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BETA DECAY RADIOISOTOPES, BETA-MINUS DECAY RADIOISOTOPES, DRUGS, HOURS LIVING RADIOISOTOPES, INTERMEDIATE MASS NUCLEI, INTERNAL CONVERSION RADIOISOTOPES, ISOMERIC TRANSITION ISOTOPES, ISOTOPES, LABELLED COMPOUNDS, MATERIALS, NUCLEI, ODD-EVEN NUCLEI, RADIOACTIVE MATERIALS, RADIOISOTOPES, TECHNETIUM ISOTOPES, YEARS LIVING RADIOISOTOPES
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