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https://www.readbyqxmd.com/read/29774904/investigating-subtle-4f-vs-5f-coordination-differences-using-kinetically-inert-eu-iii-tb-iii-and-cm-iii-complexes-of-a-coumarin-appended-1-4-7-10-tetraazacyclododecane-1-4-7-triacetate-do3a-ligand
#1
Anne Kathrine R Junker, Gauthier J-P Deblonde, Rebecca J Abergel, Thomas Just Sørensen
In order to reveal subtle differences between the solution chemistries of trivalent 4f and 5f elements, the physicochemical and photophysical properties of europium(iii), terbium(iii) and curium(iii) complexes formed with a 7-methoxy-coumarin appended 1,4,7,10-tetraazadodecane-1,4,7-triacid (DO3A) ligand were studied. All three complexes were found to be kinetically inert and exhibit stability constants similar to their 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) equivalents. The Cm(iii) and Eu(iii) complexes feature strong sensitised emission, while the triplet energy of the coumarin prohibits efficient sensitisation of the Tb(iii) analogue...
May 18, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/29756137/ros-responsive-mesoporous-silica-nanoparticles-for-mr-imaging-guided-photodynamically-maneuvered-chemotherapy
#2
Vijayakameswara Rao N, Hwa Seung Han, Hansang Lee, Van Quy Nguyen, Sangmin Jeon, Dae-Woong Jung, Jeongjin Lee, Gi-Ra Yi, Jae Hyung Park
Mesoporous silica nanoparticles (MSNs) with stimuli-responsive gatekeepers have been extensively investigated for controlled drug delivery at the target sites. Herein, we developed reactive oxygen species (ROS)-responsive MSNs (R-MSNs), consisting of a gadolinium (Gd)-DOTA complex as the ROS-responsive gatekeeper and polyethylene glycol (PEG)-conjugated chlorin e6 as the ROS generator, for magnetic resonance (MR) imaging-guided photodynamic chemotherapy. Doxorubicin (DOX), chosen as an anticancer drug, was physically encapsulated into DOTA-conjugated MSNs, followed by chemical crosslinking via the addition of GdCl3...
May 14, 2018: Nanoscale
https://www.readbyqxmd.com/read/29746106/improved-efficacy-of-synthesizing-m-iii-labeled-dota-complexes-in-binary-mixtures-of-water-and-organic-solvents-a-combined-radio-and-physicochemical-study
#3
Marylaine Pérez-Malo, Gergely Szabó, Elisabeth Eppard, Adrienn Vagner, Ernő Brücher, Imre Tóth, Alessandro Maiocchi, Eul Hyun Suh, Zoltán Kovács, Zsolt Baranyai, Frank Rösch
Typically, the synthesis of radiometal-based radiopharmaceuticals is performed in buffered aqueous solutions. We found that the presence of organic solvents like ethanol increased the radiolabeling yields of [68 Ga]Ga-DOTA (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacatic acid). In the present study, the effect of organic cosolvents [ethanol (EtOH), isopropyl alcohol, and acetonitrile] on the radiolabeling yields of the macrocyclic chelator DOTA with several trivalent radiometals (gallium-68, scandium-44, and lutetium-177) was systematically investigated...
May 10, 2018: Inorganic Chemistry
https://www.readbyqxmd.com/read/29745348/automated-synthesis-of-68ga-dota-toc-methodological-aspects-and-suitable-technical-solutions-for-a-cationic-purification-system
#4
Licia Uccelli, Alessandra Boschi, Corrado Cittanti, Petra Martini, Luca Lodi, Elisa Zappaterra, Simona Romani, Samanta Zaccaria, Davide Cecconi, Ilaria Rambaldi, Ivan Santi, Stefano Panareo, Melchiore Giganti, Mirco Bartolomei
The PET Gallium-68 isotope has the advantage of being produced from a generator, so it is also available in nuclear medicine departments without a cyclotron. The preparation of Ga-68 DOTA-labelled compounds is actually performed by remotely controlled automated systems developed in order to assure production efficiency, reproducibility of the results, guarantee fast reaction time, to facilitate the synthesis and minimize the radiation exposure. Many automatic synthesis systems are available on the radiopharmaceutical market, and each of these requires the realization of some technical adaptations for routine use...
May 8, 2018: Current Radiopharmaceuticals
https://www.readbyqxmd.com/read/29741215/role-of-dotatate-pet-ct-in-preoperative-assessment-of-phaeochromocytoma-and-paragangliomas
#5
Matti L Gild, Nikita Naik, Jeremy Hoang, Edward Hsiao, Rachel T McGrath, Mark Sywak, Stan Sidhu, Leigh Walter Delbridge, Bruce Gregory Robinson, Geoff Schembri, Roderick John Clifton-Bligh
CONTEXT: Diagnosis of paragangliomas (PGL) and phaeochromocytomas (PC) can be challenging particularly if the tumour is small. Detection of metastatic disease is important for comprehensive management of malignant PC/PGL. Somatostatin receptor imaging (SRI) agents have high sensitivity for these tumours, particularly the DOTA family of radiopharmaceuticals labelled with 68 Gallium. OBJECTIVE: To describe the utility of SRI in primary assessment (i.e. before surgery) for PC/PGL and whether measures of maximum standardized uptake (SUVmax) could be used to distinguish between adrenal adenomas and PCs...
May 9, 2018: Clinical Endocrinology
https://www.readbyqxmd.com/read/29741203/peptide-receptor-radionuclide-therapy-for-advanced-gastroenteropancreatic-neuroendocrine-tumors-from-oncology-perspective
#6
Agnieszka Kolasińska-Ćwikła, Anna Łowczak, Katarzyna Maciejkiewicz Maciejkiewicz, Jarosław Bogdan Ćwikła
Peptide Receptor Radionuclide Therapy (PRRT) is a form of molecular targeted therapy which is performed by using a small peptide (somatostatin analogue - SSA) that is coupled with a radionuclide beta emitting radiation. PRRT is a nuclear medicine for the systemic treatment of non-resectable, metastasized well/moderately differentiated, neuroendocrine tumours (NET) with overexpression of somatostatin receptor. These types of tumours include gastroenteropancreatic neoplasm (GEP-NENs), e.g. arising from the small bowel (often called carcinoid tumours), the pancreas, duodenum or stomach, but also from the large bowel or the lung and many other tissues (so called diffuse neuroendocrine system)...
2018: Nuclear Medicine Review. Central & Eastern Europe
https://www.readbyqxmd.com/read/29736890/a-tutorial-on-model-informed-approaches-to-cardiovascular-safety-with-focus-on-cardiac-repolarisation
#7
S Y A Cheung, J Parkinson, U Wählby-Hamrén, C D Dota, Å M Kragh, L Bergenholm, T Vik, T Collins, C Arfvidsson, C E Pollard, H K Tomkinson, B Hamrén
Drugs can affect the cardiovascular (CV) system either as an intended treatment or as an unwanted side effect. In both cases, drug-induced cardiotoxicities such as arrhythmia and unfavourable hemodynamic effects can occur, and be described using mathematical models; such a model informed approach can provide valuable information during drug development and can aid decision-making. However, in order to develop informative models, it is vital to understand CV physiology. The aims of this tutorial are to present (1) key background biological and medical aspects of the CV system, (2) CV electrophysiology, (3) CV safety concepts, (4) practical aspects of development of CV models and (5) regulatory expectations with a focus on using model informed and quantitative approaches to support nonclinical and clinical drug development...
May 7, 2018: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/29729071/syntheses-and-evaluation-of-68-ga-and-153-sm-labeled-dota-conjugated-bisphosphonate-ligand-for-potential-use-in-detection-of-skeletal-metastases-and-management-of-pain-arising-from-skeletal-metastases
#8
Sudipta Chakraborty, Dibakar Goswami, Rubel Chakravarty, Shahiralam Khan Mohammed, H D Sarma, Ashutosh Dash
This article reports the syntheses and evaluation of 68 Ga- and 153 Sm-complexes of a new DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid)-conjugated geminal bisphosphonate, DOTA-Bn-SCN-BP, for their potential uses in the early detection of skeletal metastases by imaging and palliation of pain arising from skeketal metastases, respectively. The conjugate was synthesized in high purity following an easily adaptable three step reaction scheme. Gallium-68- and 153 Sm-complexes were prepared in high yield (>98%) and showed excellent in vitro stability in phosphate buffered slaine (PBS) and human serum...
May 5, 2018: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29721070/tumor-targeted-dual-modality-imaging-to-improve-intraoperative-visualization-of-clear-cell-renal-cell-carcinoma-a-first-in-man-study
#9
Marlène C Hekman, Mark Rijpkema, Constantijn H Muselaers, Egbert Oosterwijk, Christina A Hulsbergen-Van de Kaa, Otto C Boerman, Wim J Oyen, Johan F Langenhuijsen, Peter F Mulders
Intraoperative imaging with antibodies labeled with both a radionuclide for initial guidance and a near-infrared dye for adequate tumor delineation may overcome the main limitation of fluorescence imaging: the limited penetration depth of light in biological tissue. In this study, we demonstrate the feasibility and safety of intraoperative dual-modality imaging with the carbonic anhydrase IX (CAIX)-targeting antibody 111 In-DOTA-girentuximab-IRDye800CW in clear cell renal cell carcinoma (ccRCC) patients. Methods: A phase I protein dose escalation study was performed in patients with a primary renal mass who were scheduled for surgery...
2018: Theranostics
https://www.readbyqxmd.com/read/29718660/coordination-properties-of-gddo3a-based-model-compounds-of-bioresponsive-mri-contrast-agents
#10
Serhat Gündüz, Sandip Vibhute, Richard Botár, Ferenc K Kálmán, Imre Tóth, Gyula Tircsó, Martín Regueiro-Figueroa, David Esteban-Gómez, Carlos Platas-Iglesias, Goran Angelovski
We report a detailed characterization of the thermodynamic stability and dissociation kinetics of Gd3+ complexes with DO3A derivatives containing a (methylethylcarbamoylmethylamino)acetic acid (L1 ), (methylpropylcarbamoylmethylamino)acetic acid (L2 ), 2-dimethylamino- N-ethylacetamide (L3 ), or 2-dimethylamino- N-propylacetamide (L4 ) group attached to the fourth nitrogen atom of the macrocyclic unit. These ligands are model systems of Ca2+ - and Zn2+ -responsive contrast agents (CA) for application in magnetic resonance imaging (MRI)...
May 2, 2018: Inorganic Chemistry
https://www.readbyqxmd.com/read/29713764/novel-use-of-177-lu-dota-rgd-2-in-treatment-of-68-ga-dota-rgd-2-avid-lesions-in-papillary-thyroid-cancer-with-tenis
#11
Ashwin Singh Parihar, Ashwani Sood, Rajender Kumar, Priya Bhusari, Jaya Shukla, Bhagwant Rai Mittal
No abstract text is available yet for this article.
May 1, 2018: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29713762/prolonged-survival-in-secondary-glioblastoma-following-local-injection-of-targeted-alpha-therapy-with-213-bi-substance-p-analogue
#12
Leszek Krolicki, Frank Bruchertseifer, Jolanta Kunikowska, Henryk Koziara, Bartosz Królicki, Maciej Jakuciński, Dariusz Pawlak, Christos Apostolidis, Saed Mirzadeh, Rafał Rola, Adrian Merlo, Alfred Morgenstern
BACKGROUND: Glioblastoma multiforme (GBM), the most common malignant brain tumor, mainly manifests as a primary de novo and less frequently as a secondary glial neoplasm. GBM has been demonstrated to overexpress the NK-1 receptor and substance P can be used as a ligand for targeted therapy. Alpha emitters, e.g. 213 Bi, that deposit their high energy within a short range allow the selective irradiation of tumor cells while sparing adjacent neuronal structures. MATERIAL AND METHODS: Among 50 glioma patients of different subtypes that have to date been treated with targeted alpha therapy at the Medical University Warsaw, we report here the data on nine patients with secondary GBM...
April 30, 2018: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29704772/mass-spectrometry-characterization-of-dota-nimotuzumab-conjugate-as-precursor-of-an-innovative-%C3%AE-tracer-suitable-in-radio-guided-surgery
#13
Claudia Martelli, Valeria Marzano, Federica Marini, Teresa Scotognella, Ilaria Fratoddi, Iole Venditti, Dante Rotili, Elena Solfaroli-Camillocci, Francesco Collamati, Carlo Mancini-Terracciano, Silvio Morganti, Daria Maccora, Riccardo Faccini, Antonella Cartoni, Alessandro Giordano, Massimo Castagnola
The aim of the present work has been the mass spectrometry characterization of the Nimotuzumab (NIM) antibody chemically modified with the bifunctional chelating agent para-S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraaza cyclododecanetetraacetic acid (p-SCN-Bn-DOTA). The conjugate, upon labeling with the pure β- -emitter 90 Y3+ , could represent a promising candidate as radiotracer for an innovative radio-guided surgery (RGS) technique, developed and patented by researchers of our group, which uses a probe system for intraoperative detection of tumor residues exploiting the selective uptake of β- -emitting tracers...
March 12, 2018: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29701218/synthesis-of-c-functionalized-te1pa-and-comparison-with-its-analogues-an-example-of-bioconjugation-on-9e7-4-mab-for-multiple-myeloma-64-cu-pet-imaging
#14
Thomas Le Bihan, Anne-Sophie Navarro, Nathalie Le Bris, Patricia Le Saëc, Sébastien Gouard, Ferid Haddad, Jean-François Gestin, Michel Chérel, Alain Faivre-Chauvet, Raphaël Tripier
In view of the excellent copper(ii) and 64-copper(ii) complexation of a TE1PA ligand, a monopicolinate cyclam, in both aqueous medium and in vivo, we looked for a way to make it bifunctional, while maintaining its chelating properties. Overcoming the already known drawback of grafting via its carboxyl group, which is essential to the overall properties of the ligand, a TE1PA bifunctional derivative bearing an additional isothiocyanate coupling function on a carbon atom of the macrocyclic ring was synthesized...
April 27, 2018: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/29687324/imaging-vegf-receptors-and-%C3%AE-v-%C3%AE-3-integrins-in-a-mouse-hindlimb-ischemia-model-of-peripheral-arterial-disease
#15
Yared Tekabe, Qing Li, Geping Zhang, Jordan Johnson, Ann Marie Schmidt, Marina Backer, Joseph Backer, Lynne L Johnson
PURPOSE: To compare targeted imaging of vascular endothelial growth factor (VEGF) receptors vs. αv β3 integrins in a mouse hindlimb ischemia model of peripheral artery disease. PROCEDURES: Male wild-type (WT) C57BL/6 mice (8- to 10-week old) (n = 24) underwent left femoral artery ligation. The right leg served as control. Five days later, mice were injected with either VEGF receptor targeting [99m Tc]DOTA-PEG-scVEGF ([99m Tc]scV) (n = 8) or with αv β3 -targeting tracer [99m Tc]HYNIC-cycloRGD ([99m Tc]RGD) (n = 8) and underwent single photon emission computed tomography (SPECT) x-ray computed tomography imaging...
April 23, 2018: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/29687322/optimization-of-a-labeling-and-kit-preparation-method-for-ga-68-labeled-dotatate-using-cation-exchange-resin-purified-ga-68-eluates-obtained-from-a-tin-dioxide-68-ge-68-ga-generator
#16
Deidré Prince, Daniel Rossouw, Sietske Rubow
PURPOSE: The aim of this study was to optimize a radiolabeling method using cationic processed Ga-68 eluates from a SnO2 -based 68 Ge/68 Ga generator, followed by the development of DOTA-Tyr3 -Thre8 -octreotide (DOTATATE) kits. PROCEDURES: Diluted generator eluates were adsorbed on a SCX resin and desorbed with acidified 5 M NaCl solution. Optimized labeling conditions were determined by variation of pH, using 35 μg DOTATATE and sodium acetate buffer. DOTATATE kits were developed based on optimized radiolabeling conditions, were labeled, and evaluated...
April 23, 2018: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/29684274/preclinical-development-of-novel-psma-targeting-radioligands-modulation-of-albumin-binding-properties-to-improve-prostate-cancer-therapy
#17
Christoph A Umbricht, Martina Benešová, Roger Schibli, Cristina Müller
The treatment of metastatic castration-resistant prostate cancer (mCRPC) remains challenging with current treatment options. The development of more effective therapies is, therefore, urgently needed. Targeted radionuclide therapy with prostate-specific membrane antigen (PSMA)-targeting ligands has revealed promising clinical results. In an effort to optimize this concept, it was the aim of this study to design and investigate PSMA ligands comprising different types of albumin binders. PSMA-ALB-53 and PSMA-ALB-56 were designed by combining the glutamate-urea-based PSMA-binding entity, a DOTA chelator and an albumin binder based on the 4-( p-iodophenyl)-moiety or p-(tolyl)-moiety...
May 2, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29683101/in-vivo-evaluation-of-free-and-chelated-accelerator-produced-actinium-225-radiation-dosimetry-and-toxicity-results
#18
Zewei Jiang, Ekaterina Revskaya, Darrell R Fisher, Ekaterina Dadachova
OBJECTIVE: The demand for the alpha-emitting radionuclide Actinium-225 (225Ac) for use in radionuclide therapy is growing. Producing 225Ac using high energy linear accelerators, cyclotrons or photoinduction could increase its supply. One potential problem with accelerator produced 225Ac using Thorium-232 targets is the presence in final product of 0.1-0.3% by activity of the long-lived 227Ac impurity at the end of irradiation. It is important to comprehensively evaluate the behavior of accelerator-produced 225Ac in vivo before using it in pre-clinical and clinical applications...
April 23, 2018: Current Radiopharmaceuticals
https://www.readbyqxmd.com/read/29674421/anti-misrii-radiolabeled-antibodies-new-tools-for-a-theranostic-approach-in-ovarian-cancer
#19
Emmanuel Deshayes, Riad Ladjohounlou, Pierre Le Fur, Alexandre Pichard, Catherine Lozza, Vincent Boudousq, Samuel Sevestre, Marta Jarlier, Roxana Kashani, Joanna Koch, Jane Sosabowski, Julie Foster, Nicolas Chouin, Frank Bruchertseifer, Alfred Morgenstern, Pierre-Olivier Kotzki, Isabelle Navarro-Teulon, Jean-Pierre Pouget
We have developed the 16F12 mouse monoclonal antibody (mAb) that targets the MISRII receptor expressed by ovarian tumors. Here, we assessed in preclinical models the possibility to use radiolabeled 16F12 in a theranostic approach for small-volume ovarian peritoneal carcinomatosis, for instance after cytoreductive surgery. Methods: DOTA-, DTPA- or DFO-conjugated 16F12 mAb was radiolabeled with beta (177 Lu) or alpha (213 Bi) particle emitters for therapeutic use, and with 89 Zr for positron emission tomography (PET) imaging...
April 19, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29674419/comparative-study-of-the-novel-rgd-motif-containing-itg%C3%AE-v%C3%AE-6-binding-peptides-sflap3-and-sfitgv6-for-diagnostic-application-in-hnscc
#20
Saskia Roesch, Thomas Lindner, Max Sauter, Anastasia Loktev, Paul Flechsig, Martin Müller, Walter Mier, Rolf Warta, Gerhard Dyckhoff, Christel Herold-Mende, Uwe Haberkorn, Annette Altmann
Alpha v beta 6 (αvβ6) integrin is overexpressed by several carcinomas, and thus considered as target for diagnostic imaging and anti-cancer therapies. Recently, we presented SFITGv6 as a novel potential tracer for imaging and targeted therapy of αvβ6 integin-positive carcinomas. Here, we analyzed affinity and specificity of five native αvβ6 integrin-specific binders in comparison to SFITGv6. Methods: Sunflower trypsin inhibitor (SFTI)-1-based peptides containing arginine-glycine-aspartic acid (RGD) motif-spanning octamers of fibronectin (SFFN1), tenascin C (SFTNC), vitronectin (SFVTN), and latency-associated peptides (LAP) 1 (SFLAP1), and 3 (SFLAP3) were synthesized and their binding potential to αvβ6 integrin-expressing head and neck squamous cell carcinoma (HNSCC) cell lines was evaluated...
April 19, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
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