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https://www.readbyqxmd.com/read/28636973/amide-to-triazole-switch-vs-in-vivo-nep-inhibition-approaches-to-promote-radiopeptide-targeting-of-grpr-positive-tumors
#1
Theodosia Maina, Aikaterini Kaloudi, Ibai E Valverde, Thomas L Mindt, Berthold A Nock
INTRODUCTION: Radiolabeled bombesin (BBN)-analogs have been proposed for diagnosis and therapy of gastrin-releasing peptide receptor (GRPR)-expressing tumors, such as prostate, breast and lung cancer. Metabolic stability represents a crucial factor for the success of this approach by ensuring sufficient delivery of circulating radioligand to tumor sites. The amide-to-triazole switch on the backbone of DOTA-PEG4-[Nle(14)]BBN(7-14) (1) was reported to improve the in vitro stability of resulting (177)Lu-radioligands...
June 10, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28631929/-13-c-dynamic-nuclear-polarization-using-a-trimeric-gd-3-complex-as-an-additive
#2
Peter Niedbalski, Christopher Parish, Qing Wang, Andhika Kiswandhi, Zahra Hayati, Likai Song, Lloyd Laporca Lumata
Dissolution dynamic nuclear polarization (DNP) is one of the most successful techniques that resolves the insensitivity problem in liquid-state nuclear magnetic resonance (NMR) spectroscopy and imaging (MRI) by amplifying the signal by several thousand-fold. One way to further improve the DNP signal is the inclusion of trace amounts of lanthanides in DNP samples doped with trityl OX063 free radical as the polarizing agent. In practice, stable monomeric gadolinium complexes such as Gd-DOTA or Gd-HP-DO3A are used as beneficial additives in DNP samples, further boosting the DNP-enhanced solid-state 13C polarization by a factor of 2 or 3...
June 20, 2017: Journal of Physical Chemistry. A
https://www.readbyqxmd.com/read/28628723/new-multifunctional-radiotheranostic-agent-for-dual-targeting-of-breast-cancer-cells
#3
Filipe Vultos, Célia Fernandes, Filipa Mendes, Fernanda Marques, João Correia, Isabel Santos, Lurdes Gano
A straightforward synthetic route for a new multifunctional DOTA derivative is described. To prove the versatility of this prochelator to prepare radiolabelled hybrid compounds containing two different biological targeting moieties, an antitumoral agent (e.g. DNA intercalating agent) and an Estrogen Receptor ligand (e.g. LXXLL based peptide) were regiospecifically conjugated to the DOTA derivative. The bifunctional probe was radiolabelled with the Auger electron emitter Indium-111 and the radioconjugate demonstrated to induce DNA damage in vitro which along with the nuclear internalization exhibited in breast cancer cells might enhance its therapeutic activity...
June 19, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28627868/alkaline-phosphatase-instructed-self-assembly-of-gadolinium-nanofibers-for-enhanced-t2-weighted-magnetic-resonance-imaging-of-tumor
#4
Ling Dong, Junchao Qian, Zijuan Hai, Jinyong Xu, Wei Du, Kai Zhong, Gaolin Liang
Alkaline phosphatase (ALP) is an important enzyme but using ALP-instructed self-assembly of gadolinium nanofibers for enhanced T2-weighted magnetic resonance imaging (MRI) of tumor has not been reported. In this work, we rationally designed a hydrogelator Nap-FFFYp-EDA-DOTA(Gd) (1P) which, under the catalysis of ALP, was able to self-assemble into gadolinium nanofibers to form hydrogel Gel I for enhanced T2-weighted MR imaging of ALP activity in vitro and in tumor. T2 phantom MR imaging indicated that the transverse relaxivity (r2) value of Gel I was 33...
June 21, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28627037/quantitative-gd-dota-uptake-from-cerebrospinal-fluid-into-rat-brain-using-3d-vfa-spgr-at-9-4t
#5
Hedok Lee, Kristian Mortensen, Simon Sanggaard, Palle Koch, Hans Brunner, Bjørn Quistorff, Maiken Nedergaard, Helene Benveniste
PURPOSE: We propose a quantitative technique to assess solute uptake into the brain parenchyma based on dynamic contrast-enhanced MRI (DCE-MRI). With this approach, a small molecular weight paramagnetic contrast agent (Gd-DOTA) is infused in the cerebral spinal fluid (CSF) and whole brain gadolinium concentration maps are derived. METHODS: We implemented a 3D variable flip angle spoiled gradient echo (VFA-SPGR) longitudinal relaxation time (T1) technique, the accuracy of which was cross-validated by way of inversion recovery rapid acquisition with relaxation enhancement (IR-RARE) using phantoms...
June 19, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/28625749/preclinical-evaluation-of-melanocortin-1-receptor-mc1-r-specific-68-ga-and-44-sc-labeled-dota-napamide-in-melanoma-imaging
#6
Gábor Nagy, Noémi Dénes, Adrienn Kis, Judit P Szabó, Ervin Berényi, Ildikó Garai, Péter Bai, István Hajdu, Dezső Szikra, György Trencsényi
PURPOSE: Alpha melanocyte stimulating hormone (α-MSH) enhances melanogenesis in melanoma malignum by binding to melanocortin-1 receptors (MC1-R). Earlier studies demonstrated that alpha-MSH analog NAPamide molecule specifically binds to MC1-R receptor. Radiolabeled NAPamide is a promising radiotracer for the non-invasive detection of melanin producing melanoma tumors by Positron Emission Tomography (PET). In this present study the MC1-R selectivity of the newly developed Sc-44-labeled DOTA-NAPamide was investigated in vitro and in vivo using melanoma tumors...
June 15, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28620681/cardiac-t1-mapping-in-congenital-heart-disease-bolus-vs-infusion-protocols-for-measurements-of-myocardial-extracellular-volume-fraction
#7
Nadya Al-Wakeel-Marquard, Sanaz Rastin, Frédéric Muench, Darach O H-Ici, Sevim Yilmaz, Felix Berger, Titus Kuehne, Daniel R Messroghli
Myocardial extracellular volume fraction (ECV) reflecting diffuse myocardial fibrosis can be measured with T1 mapping cardiovascular magnetic resonance (CMR) before and after the application of a gadolinium-based extracellular contrast agent. The equilibrium between blood and myocardium contrast concentration required for ECV measurements can be obtained with a primed contrast infusion (equilibrium contrast-CMR). We hypothesized that equilibrium can also be achieved with a single contrast bolus to accurately measure diffuse myocardial fibrosis in patients with congenital heart disease (CHD)...
June 15, 2017: International Journal of Cardiovascular Imaging
https://www.readbyqxmd.com/read/28618966/-68-ga-177-lu-labeled-dota-tate-shows-similar-imaging-and-biodistribution-in-neuroendocrine-tumor-model
#8
Fei Liu, Hua Zhu, Jiangyuan Yu, Xuedi Han, Qinghua Xie, Teli Liu, Chuanqin Xia, Nan Li, Zhi Yang
Somatostatin receptors are overexpressed in neuroendocrine tumors, whose endogenous ligands are somatostatin. DOTA-TATE is an analogue of somatostatin, which shows high binding affinity to somatostatin receptors. We aim to evaluate the (68)Ga/(177)Lu-labeling DOTA-TATE kit in neuroendocrine tumor model for molecular imaging and to try human-positron emission tomography/computed tomography imaging of (68)Ga-DOTA-TATE in neuroendocrine tumor patients. DOTA-TATE kits were formulated and radiolabeled with (68)Ga/(177)Lu for (68)Ga/(177)Lu-DOTA-TATE (M-DOTA-TATE)...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28605448/efficacy-of-peptide-receptor-radionuclide-therapy-prrt-for-functional-metastatic-paraganglioma-and-phaeochromocytoma
#9
Grace Kong, Simona Grozinsky-Glasberg, Michael S Hofman, Jason Callahan, Amichay Meirovitz, Ofra Maimon, David A Pattison, David J Gross, Rodney J Hicks
Purpose: Treatment options for unresectable Paraganglioma (PGL)/Phaeochromocytoma (PCC), especially with uncontrolled secondary hypertension (HTN) are limited. Preliminary studies with PRRT suggest efficacy but data on HTN control and survival are lacking. We assessed PRRT outcomes in such patients from 2 referral centres. Methods: 20 consecutive patients (M:F=13:7; 21-77y.o.) with high somatostatin receptor (SSTR) expression treated with 177Lu-DOTA-octreotate, 9 with radiosensitising chemotherapy, were retrospectively reviewed...
June 9, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28598691/development-of-68-ga-scn-dota-capsaicin-as-an-imaging-agent-targeting-apoptosis-and-cell-cycle-arrest-in-breast-cancer
#10
Jun Young Lee, Sang-Yeun Lee, Gun Gyun Kim, Min Goo Hur, Seung Dae Yang, Jeong-Hoon Park, Sang Wook Kim
(68)Ga-labeled capsaicin using a DOTA (1,4,7,10-tetraazocyclododecane-N,N',N″,N'″-tetraacetic acid) derivative [(68)Ga-SCN-Benzyl(Bn)-DOTA-capsaicin] was studied for the diagnosis of breast cancers, such as MCF-7 and SK-BR-3. The standard compound, (69)Ga-SCN-Bn-DOTA-capsaicin, was also prepared and characterized by spectroscopic analysis. The binding affinity of (68)Ga-SCN-Bn-DOTA-capsaicin was evaluated by using breast cancer cell lines (MCF-7, SK-BR-3) and colon cancer cell (CT-26); the biodistribution was carried out by using MCF-7-bearing nude mice, after which the positron emission tomography (PET) images were obtained at different time intervals (15-120 minutes)...
June 2017: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28595014/a-chelator-free-and-biocompatible-melanin-nanoplatform-with-facile-loading-gadolinium-and-copper-64-for-bioimaging
#11
Su Hyun Hong, Yao Sun, Chu Tang, Kai Cheng, Ruiping Zhang, Quli Fan, Liying Xu, Daijuan Huang, Anthony Zhao, Zhen Cheng
Development of a chelator-free and biocompatible platform for facile construction of gadolinium3+ (Gd3+) loaded nanoparticle-based probe for in vivo magentic resonance imaging (MRI) is still challenging. Herein, a biocompatible Gd3+ loaded melanin dot (Gd-M-dot) has been easily preppared without the use of ay chelators, and the resulted nanoprobe exhibited good loading efficiency for Gd3+, high stability, and higher T1 relaxivity compared with the commercial contrast agent, Gd-DOTA. Furthermore, Gd-M-dot showed unique photoacoustic (PA) property, and high PA imaging signal could be observed after 1 h injection in small animal models...
June 8, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28587822/initial-evaluation-of-cu-64-labeled-parpi-dota-pet-imaging-in-mice-with-mesothelioma
#12
Tao Huang, Pengcheng Hu, Anna B Banizs, Jiang He
Poly(ADP-ribose) polymerase (PARP) has emerged as an important molecular target for the treatment of several oncological diseases. A couple of molecular probes based on Olaparib scaffold have been developed by incorporation of F-18 or fluorophore for positron emission tomography (PET) or optical imaging in several types of tumor. PARP has been reported overexpressed in mesothelioma. We hereby synthesized an analogue of Olaparib containing DOTA moiety and radiolabeled it with Cu-64 to evaluate its utility of PET tracer for mesothelioma...
May 26, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28577300/application-of-higher-energy-collisional-dissociation-hcd-to-the-fragmentation-of-new-dota-based-labels-and-n-termini-dota-labeled-peptides
#13
A H El-Khatib, Y He, D Esteban-Fernández, M W Linscheid
DOTA derivatives are applied in quantitative proteomics owing to their ability to react with different functional groups, to harbor lanthanoides and hence their compatibility with molecular and elemental mass spectrometry. The new DOTA derivatives, namely Ln-MeCAT-Click and Ln-DOTA-Dimedone, allow efficient thiol labeling and targeting sulfenation as an important post-translational modification, respectively. Quantitative applications require the investigation of fragmentation behavior of these reagents. Therefore, the fragmentation behavior of Ln-MeCAT-Click and Ln-DOTA-Dimedone was studied using collision-induced dissociation (CID), infrared multiphoton dissociation (IRMPD) and higher-energy collision dissociation (HCD) using different energy levels and the efficiency of reporter ion production was estimated...
June 2, 2017: Journal of Mass Spectrometry: JMS
https://www.readbyqxmd.com/read/28572490/a-modular-dual-labeling-scaffold-that-retains-agonistic-properties-for-somatostatin-receptor-targeting
#14
Sukhen C Ghosh, Melissa Rodriguez, Kendra S Carmon, Julie Voss, Nathaniel L Wilganowski, Agnes Schonbrunn, Ali Azhdarinia
Fluorescence-guided surgery is an emerging imaging technique that can enhance the ability of surgeons to detect tumors when compared with visual observation. To facilitate characterization, fluorescently labeled probes have been dual-labeled with a radionuclide to enable cross-validation with nuclear imaging. In this study, we selected the somatostatin receptor (SSTR) imaging agent, DOTA-Phe1-Tyr3-octreotide (DOTA-TOC), as the foundation for developing a dual-labeled analog. We hypothesized that a customized dual labeling approach with a multimodality chelation (MMC) scaffold would minimize steric effects of dye conjugation and retain agonist properties...
June 1, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28556976/exploring-the-radiosynthesis-and-in-vitro-characteristics-of-68-ga-ga-dota-siglec-9
#15
Svend B Jensen, Meeri Käkelä, Lars Jødal, Olli Moisio, Aage K O Alstrup, Sirpa Jalkanen, Anne Roivainen
Vascular adhesion protein 1 is a leukocyte homing-associated glycoprotein, which upon inflammation rapidly translocates from intracellular sources to the endothelial cell surface. It has been discovered that the cyclic peptide residues 283-297 of sialic acid-binding IgG-like lectin 9 (Siglec-9) "CARLSLSWRGLTLCPSK" bind to vascular adhesion protein 1 and hence makes the radioactive analogues of this compound ([(68) Ga]Ga-DOTA-Siglec-9) interesting as a noninvasive visualizing marker of inflammation. Three different approaches to the radiosynthesis of [(68) Ga]Ga-DOTA-Siglec-9 are presented and compared with previously published methods...
May 30, 2017: Journal of Labelled Compounds & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28553510/model-free-extraction-of-spin-label-position-distributions-from-pseudocontact-shift-data
#16
Elizaveta A Suturina, Daniel Häussinger, Kaspar Zimmermann, Luca Garbuio, Maxim Yulikov, Gunnar Jeschke, Ilya Kuprov
A significant problem with paramagnetic tags attached to proteins and nucleic acids is their conformational mobility. Each tag is statistically distributed within a volume between 5 and 10 Angstroms across; structural biology conclusions from NMR and EPR work are necessarily diluted by this uncertainty. The problem is solved in electron spin resonance, but remains open in the other major branch of paramagnetic resonance - pseudocontact shift (PCS) NMR spectroscopy, where structural biologists have so far been reluctantly using the point paramagnetic centre approximation...
April 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28553181/initial-clinical-experience-with-68-ga-dota-noc-prepared-using-68-ga-from-nanoceria-polyacrylonitrile-composite-sorbent-based-68-ge-68-ga-generator-and-freeze-dried-dota-noc-kits
#17
Piyush Chandra, Bhakti Shetye, Rubel Chakravarty, Archana Mukherjee, Usha Pandey, Ashish Kumar Jha, Nilendu Purandare, Sneha Shah, Archi Agrawal, Ramu Ram, Ashutosh Dash, Venkatesh Rangarajan
Somatostatin receptor positron emission tomography-computed tomography (PET/CT) with (68)Ga-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) peptides have become an indispensable part of disease assessment in patients with neuroendocrine tumors and forms the basis of personalized therapy with peptide receptor-based radionuclide therapy. With growing utilization of PET/CT in developing countries, availability of the indigenous GMP-certified (68)Ge/(68)Ga generators is expected to further promote cost-effective molecular imaging service to the cancer patients...
April 2017: World Journal of Nuclear Medicine
https://www.readbyqxmd.com/read/28553179/peptide-receptor-radionuclide-therapy-with-177-lu-dotatate-for-metastatic-neuroendocrine-tumor-occurring-in-association-with-multiple-endocrine-neoplasia-type-1-and-cushing-s-syndrome
#18
Chinna Naik, Sandip Basu
Neuroendocrine tumor (NET) occurring in association with other endocrine syndromes forms a distinct entity. The aim was to assess the therapy response profile of the routine peptide receptor radionuclide therapy (PRRT) in this relatively uncommon but clinically challenging subgroup of patients. A retrospective analysis was undertaken from the case records from those who were treated with (177)Lu-DOTATATE for metastatic NET. In addition to assessing the therapeutic efficacy, emphasis was also given to study lesional sites and scan pattern...
April 2017: World Journal of Nuclear Medicine
https://www.readbyqxmd.com/read/28552648/ultrasmall-graphene-oxide-based-t1-mri-contrast-agent-for-in-vitro-and-in-vivo-labeling-of-human-mesenchymal-stem-cells
#19
Mengxin Zhang, Xiaoyun Liu, Jie Huang, Lina Wang, He Shen, Yu Luo, Zhenjun Li, Hailu Zhang, Zongwu Deng, Zhijun Zhang
Herein, we report on development of a two-dimensional nanomaterial graphene oxide (GO)-based T1 magnetic resonance imaging (MRI) contrast agent (CA) for in vitro and in vivo labeling of human mesenchymal stem cells (hMSCs). The CA was synthesized by PEGylation of ultrasmall GO, followed by conjugation with a chelating agent DOTA and then gadolinium(III) to form GO-DOTA-Gd complexes. Thus-prepared GO-DOTA-Gd complexes exhibited significantly improved T1 relaxivity, and the r1 value was 14.2 mM(-1)s(-1) at 11...
May 26, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28551157/synthesis-and-characterization-of-a-bimodal-nanoparticle-based-on-the-host-guest-self-assembly-for-targeted-cellular-imaging
#20
Huihui Wang, Dongsheng Sun, Han Liao, Yanfang Wang, Shan Zhao, Ying Zhang, Guojun Lv, Xiaojun Ma, Yang Liu, Guangwei Sun
Multimodal imaging provides distinct advantages over traditional single modal imaging. The combined modalities of magnetic resonance imaging (MRI) and near-infrared imaging (NIR), in particular, provide a powerful tool for tumor diagnosis. In this study, a bimodal MRI and NIR self-assembled supramolecular nanoparticle was developed via the self-assembly of host-guest interactions between hyaluronic acid-β-cyclodextrin (HA-CD) and amantadine (Ad)-modified imaging agents (Gd-DOTA and NIR cyanine dye Cy7). The supramolecular HA-CD-GC nanoparticles (NPs) were characterized by transmission electron microscopy (TEM), Zeta potential, and dynamic light-scattering (DLS) experiments...
August 15, 2017: Talanta
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