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https://www.readbyqxmd.com/read/28203088/peptide-receptor-radionuclide-therapy-in-the-management-of-gastrointestinal-neuroendocrine-tumors-efficacy-profile-safety-and-quality-of-life
#1
REVIEW
Stefano Severi, Ilaria Grassi, Silvia Nicolini, Maddalena Sansovini, Alberto Bongiovanni, Giovanni Paganelli
Peptide receptor radionuclide therapy (PRRT), developed over the last two decades, is carried out using radiopharmaceuticals such as 90Y-DOTA-Tyr3-octreotide and 177Lu-DOTA-Tyr3-octreotate (177Lu-Dotatate). These radiocompounds are obtained by labeling a synthetic somatostatin analog with a β-emitting radioisotope. The compounds differ from each other in terms of their energetic features (due to the radionuclide) and peptide receptor affinity (due to the analog) but share the common characteristic of binding specific membrane somatostatin receptors that are (generally) overexpressed in neuroendocrine neoplasms (NENs) and their metastases...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28190898/synthesis-and-opioid-receptor-binding-of-indium-iii-and-111-in-labeled-macrocyclic-conjugates-of-diprenorphine-novel-ligands-designed-for-imaging-studies-of-peripheral-opioid-receptors
#2
Shefali Srivastava, Emily A Fergason-Cantrell, Roger I Nahas, John R Lever
Radiolabeled diprenorphine (DPN) and analogs are widely used ligands for non-invasive brain imaging of opioid receptors. To develop complementary radioligands optimized for studies of the peripheral opioid receptors, we prepared a pair of hydrophilic DPN derivatives, conjugated to the macrocyclic chelator DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), for complexation with trivalent metals. The non-radioactive indium (III) complexes, tethered to the C6-oxygen position of the DPN scaffold by 6- to 9-atom spacers, displayed high affinities for binding to μ, δ and κ opioid receptors in vitro...
October 6, 2016: Tetrahedron
https://www.readbyqxmd.com/read/28184947/-neuroendocrine-tumor-therapy-netter-1-trial-177-lu-dota-tate-for-neuroendocrine-tumors
#3
T Derlin
No abstract text is available yet for this article.
February 9, 2017: Der Radiologe
https://www.readbyqxmd.com/read/28170242/eu-iii-complex-with-do3a-amino-phosphonate-ligand-as-a-concentration-independent-ph-responsive-contrast-agent-for-magnetic-resonance-spectroscopy-mrs
#4
Tereza Krchová, Vít Herynek, Andrea Gálisová, Jan Blahut, Petr Hermann, Jan Kotek
A new DOTA-like ligand H5do3aNP with a 2-[amino(methylphosphonic acid)]ethyl-coordinating pendant arm was prepared, and its coordinating properties were studied by NMR spectroscopy and potentiometry. The study revealed a rare slow exchange (on the (1)H and (31)P NMR time scale) between protonated and unprotonated complex species with a corresponding acidity constant pKA ∼ 8.0. This unusually slow time scale associated with protonation is caused by a significant geometric change from square-antiprismatic (SA) arrangement observed for protonated complex SA-[Eu(Hdo3aNP)](-) to twisted-square-antiprismatic (TSA) arrangement found for deprotonated complex TSA-[Eu(do3aNP)](2-)...
February 7, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28166150/68ga-dota-tate-pet-ct-for-molecular-imaging-of-somatostatin-receptor-expression-in-metastasizing-chordoma-comparison-with-18f-fdg
#5
Thorsten Derlin, Jan M Sohns, Katja Hueper
Chordoma is a rare slow-growing neoplasm of neuroectodermal origin, which frequently recurs after removal and has the potential to metastasize. We present the case of a 53-year-old man with metastasizing chordoma who underwent F-FDG and Ga-DOTA-TATE PET/CT for restaging of disease and for evaluation of targeted radionuclide therapy potential. On both F-FDG and Ga-DOTA-TATE PET scans, increased tracer accumulation was observed in chordoma metastases. Besides the increased glucose metabolism in chordoma, this case highlights the potential of Ga-DOTA-TATE PET/CT for restaging of chordoma as well the option of targeted radionuclide therapy in this entity...
February 3, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28145030/a-reactive-rigid-gd-iii-labeling-tag-for-in-cell-epr-distance-measurements-in-proteins
#6
Yin Yang, Feng Yang, Yan-Jun Gong, Jia-Liang Chen, Daniella Goldfarb, Xun-Cheng Su
The cellular environment of proteins differs considerably from in vitro conditions under which most studies of protein structures are carried out. Therefore, there is a growing interest in determining dynamics and structures of proteins in the cell. A key factor for in-cell distance measurements by the double electron-electron resonance (DEER) method in proteins is the nature of the used spin label. Here we present a newly designed Gd(III) spin label, a thiol-specific DOTA-derivative (DO3MA-3BrPy), which features chemical stability and kinetic inertness, high efficiency in protein labelling, a short rigid tether, as well as favorable spectroscopic properties, all are particularly suitable for in-cell distance measurements by the DEER method carried out at W-band frequencies...
February 1, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28138688/twins-in-spirit-part-iv-177-lu-%C3%A2-high%C3%A2-affinity-dotatate-a-promising-new-tracer-for-peptide-receptor-radiotherapy
#7
Claudia Brogsitter, Holger Hartmann, Gerd Wunderlich, Margret Schottelius, Hans-Jürgen Wester, Jörg Kotzerke
AIM: Besides the use of somatostatin analogues, small molecules like sunitinib and everolimus as well as conventional chemotherapy, peptide receptor radiotherapy (PRRT) using radiolabelled somatostatin analogues has gained an important role in the treatment of inoperable, metastasized neuroendocrine tumours (NET). There are various radiotracers in use. Based on our experience with the PET tracer [(68)Ga]DOTA-3-iodo-Tyr(3)-octreotate ([(68)Ga]HA-DOTATATE), a DOTATATE derivative with an increased binding affinity to hsst5, the current retrospective analysis is exploring the therapeutic potential of [(177)Lu]HA-DOTATATE...
January 31, 2017: Nuklearmedizin. Nuclear Medicine
https://www.readbyqxmd.com/read/28126683/pet-imaging-of-64-cu-dota-scfv-anti-psma-lipid-nanoparticles-lnps-enhanced-tumor-targeting-over-anti-psma-scfv-or-untargeted-lnps
#8
Patty Wong, Lin Li, Junie Chea, Melissa K Delgado, Desiree Crow, Erasmus Poku, Barbara Szpikowska, Nicole Bowles, Divya Channappa, David Colcher, Jeffrey Y C Wong, John E Shively, Paul J Yazaki
INTRODUCTION: Single chain (scFv) antibodies are ideal targeting ligands due to their modular structure, high antigen specificity and affinity. These monovalent ligands display rapid tumor targeting but have limitations due to their fast urinary clearance. METHODS: An anti-prostate membrane antigen (PSMA) scFv with a site-specific cysteine was expressed and evaluated in a prostate cancer xenograft model by Cu-64 PET imaging. To enhance tumor accumulation, the scFv-cys was conjugated to the co-polymer DSPE-PEG-maleimide that spontaneously assembled into a homogeneous multivalent lipid nanoparticle (LNP)...
January 17, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28125438/quantification-and-assessment-of-the-chemical-form-of-residual-gadolinium-in-the-brain-after-repeated-administration-of-gadolinium-based-contrast-agents-comparative-study-in-rats
#9
Thomas Frenzel, Chirag Apte, Gregor Jost, Laura Schöckel, Jessica Lohrke, Hubertus Pietsch
OBJECTIVE: Multiple clinical and preclinical studies have reported a signal intensity increase and the presence of gadolinium (Gd) in the brain after repeated administration of Gd-based contrast agents (GBCAs). This bioanalytical study in rat brain tissue was initiated to investigate whether the residual Gd is present as intact GBCA or in other chemical forms by using tissue fractionation and chromatography. MATERIALS AND METHODS: Rats were divided randomly in 6 groups of 10 animals each...
January 25, 2017: Investigative Radiology
https://www.readbyqxmd.com/read/28124595/a-sensitive-method-for-the-measurement-of-copper-at-trace-levels-using-an-hplc-based-assay
#10
Jason L J Dearling, Alan B Packard
BACKGROUND: Measurement of trace metal contamination is critical in the production of radiometals, such as 64Cu, for protein labeling. ICP-MS provides these data with high sensitivity and high specificity, but at high (instrument) cost. TETA (1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid) titration provides high sensitivity at low cost but with low specificity. A method that allowed the measurement of trace metals with high sensitivity but also at relatively low cost would, therefore, be very useful in the development of new radiometal production methods...
January 25, 2017: Current Radiopharmaceuticals
https://www.readbyqxmd.com/read/28119212/preparation-and-68-ga-radiolabeling-of-porous-zirconia-nanoparticle-platform-for-pet-ct-imaging-guided-drug-delivery
#11
Andras Polyak, Lívia Naszalyi Nagy, Judith Mihaly, Sebastian Görres, Alexander Wittneben, Ina Leiter, Jens P Bankstahl, Laszlo Sajti, Miklós Kellermayer, Miklós Zrínyi, Tobias L Ross
This paper describes the preparation of gallium-68 ((68)Ga) isotope labeled porous zirconia (ZrO2) nanoparticle (NP) platform of nearly 100nm diameter and its first pharmacokinetic and biodistribution evaluation accomplished with a microPET/CT (μPet/CT) imaging system. Objectives of the investigations were to provide a nanoparticle platform which can be suitable for specific delivery of various therapeutic drugs using surface attached specific molecules as triggering agents, and at the same time, suitable for positron emission tomography (PET) tracing of the prospective drug delivery process...
January 18, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28117023/an-overview-of-bioactive-peptides-for-in-vivo-imaging-and-therapy-in-human-diseases
#12
Anna Lucia Tornesello, Maria Lina Tornesello, Franco M Buonaguro
Radiolabeled peptides, designed to bind with high affinity receptors selectively expressed on cell membranes of different human tissues, represent valuable tools for in vivo imaging of several human diseases. Solid-phase peptide synthesis as well as availability of bifunctional chelating agents and prosthetic groups allows the production and radiolabeling of several peptide-based molecules which are useful to target specific receptors on different cancer types. Among them, octreotide and other analogues of somatostatin, vasoactive intestinal peptide, CCK analogues, bombesin, α-MSH analogues, neurotensin, exendin, RGD substance P, conjugated to appropriate chelators, such as DTPA, NOTA, DOTA or TETA, and radiolabeled with specific radionuclides, have already been translated into the clinical practice with remarkable sensitivity and diagnostic accurateness...
January 20, 2017: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/28108545/bombesin-antagonist-based-radiotherapy-of-prostate-cancer-combined-with-wst-11-vascular-targeted-photodynamic-therapy
#13
Kwanghee Kim, Hanwen Zhang, Stephen LaRosa, Sylvia Jebiwott, Pooja Desai, Simon Y Kimm, Avigdor J Scherz, Joseph A O'Donoghue, Wolfgang A Weber, Jonathan Coleman
PURPOSE: DOTA-AR, a bombesin-antagonist peptide, has potential clinical application for targeted imaging and therapy in Gastrin Releasing Peptide receptor (GRPr) positive malignancies when conjugated with a radioisotope such as 90Y. This therapeutic potential is limited by the fast washout of the conjugates from the target tumors. WST-11 (Weizmann STeba-11 drug; a negatively charged water-soluble palladium-bacteriochlorophyll derivative, Tookad® Soluble) Vascular targeted photodynamic therapy (VTP) is a local ablation approach recently approved for use in early stage prostate cancer...
January 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28107921/highly-selective-enrichment-of-phosphopeptides-using-zr-4-immobilized-titania-nanoparticles
#14
Junyong Dai, Miaode Wang, Hailong Liu
It is urgent to selectively enrich trace phosphorylated proteins or peptides from complex biological sample for mass spectrometry (MS)-based phosphoproteomics. In this study, a novel immobilized metal affinity chromatography (IMAC) material with DOTA(1,4,7,10-tetraazacyclododecane N, N', N'', N'''-tetra-acetic acid) coated on the surface of TiO2 nanomaterials and functionalized with the metal ion Zr(4+)(TiO2@DOTA-Zr) has been synthesized successfully to improve the enrichment specificity and sensitivity for phosphopeptides...
March 1, 2017: Talanta
https://www.readbyqxmd.com/read/28103285/radioiodinated-exendin-4-is-superior-to-the-radiometal-labelled-glucagon-like-peptide-1-receptor-probes-overcoming-their-high-kidney-uptake
#15
Tilman Läppchen, Roswitha Tönnesmann, Jos Eersels, Philipp T Meyer, Helmut R Maecke, Svetlana N Rylova
GLP-1 receptors are ideal targets for preoperative imaging of benign insulinoma and for quantifying the beta cell mass. The existing clinical tracers targeting GLP-1R are all agonists with low specific activity and very high kidney uptake. In order to solve those issues we evaluated GLP-1R agonist Ex-4 and antagonist Ex(9-39) radioiodinated at Tyr40 side by side with [Nle14,Lys40(Ahx-DOTA-68Ga)NH2]Ex-4 (68Ga-Ex-4) used in the clinic. The Kd, Bmax, internalization and binding kinetics of [Nle14,125I-Tyr40-NH2]Ex-4 and [Nle14,125I-Tyr40-NH2]Ex(9-39) were studied in vitro using Ins-1E cells...
2017: PloS One
https://www.readbyqxmd.com/read/28103036/paramagnetic-enhancement-of-nuclear-spin-spin-coupling
#16
Peter John Cherry, Syed Awais Rouf, Juha Vaara
We present a derivation and computations of the paramagnetic enhancement of the nuclear magnetic resonance (NMR) spin-spin coupling, which may be expressed in terms of the hyperfine coupling (HFC) and (for systems with multiple unpaired electrons) zero-field splitting (ZFS) tensors. This enhancement is formally analogous to the hyperfine contributions to the NMR shielding tensor as formulated by Kurland and McGarvey. The significance of the spin-spin coupling enhancement is demonstrated by using a combination of density-functional theory and correlated ab initio calculations, to determine the HFC and ZFS tensors, respectively, for two paramagnetic 3d metallocenes, a Cr(II)(acac)2 complex, a Co(II) pyrazolylborate complex, and a lanthanide system, Gd-DOTA...
February 9, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28102507/-44-sc-psma-617-for-radiotheragnostics-in-tandem-with-177-lu-psma-617-preclinical-investigations-in-comparison-with-68-ga-psma-11-and-68-ga-psma-617
#17
Christoph A Umbricht, Martina Benešová, Raffaella M Schmid, Andreas Türler, Roger Schibli, Nicholas P van der Meulen, Cristina Müller
BACKGROUND: The targeting of the prostate-specific membrane antigen (PSMA) is of particular interest for radiotheragnostic purposes of prostate cancer. Radiolabeled PSMA-617, a 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-functionalized PSMA ligand, revealed favorable kinetics with high tumor uptake, enabling its successful application for PET imaging ((68)Ga) and radionuclide therapy ((177)Lu) in the clinics. In this study, PSMA-617 was labeled with cyclotron-produced (44)Sc (T 1/2 = 4...
December 2017: EJNMMI Research
https://www.readbyqxmd.com/read/28101850/assessment-of-regional-pulmonary-blood-flow-using-68-ga-dota-pet
#18
Carlos Velasco, Jesus Mateo, Arnoldo Santos, Adriana Mota-Cobian, Fernando Herranz, Juan Pellico, Ruben A Mota, Samuel España, Jesus Ruiz-Cabello
BACKGROUND: In vivo determination of regional pulmonary blood flow (PBF) is a valuable tool for the evaluation of many lung diseases. In this study, the use of (68)Ga-DOTA PET for the in vivo quantitative determination of regional PBF is proposed. This methodology was implemented and tested in healthy pigs and validated using fluorescent microspheres. The study was performed on young large white pigs (n = 4). To assess the reproducibility and consistency of the method, three PET scans were obtained for each animal...
December 2017: EJNMMI Research
https://www.readbyqxmd.com/read/28099995/technical-note-fast-respiratory-motion-estimation-using-sorted-singles-without-unlist-processing-a-feasibility-study
#19
Jaewon Yang, Mehdi Khalighi, Thomas A Hope, Karen Ordovas, Youngho Seo
PURPOSE: The study aims to demonstrate the feasibility of fast respiratory motion estimation using singles data available as a sorted format in list-mode files acquired in an integrated PET/MRI system for a proof-of-concept. METHODS: The derivation of SDRM is enabled by singles recorded and binned by second for each detector crystal in PET list-mode data acquired in a SIGNA PET/MR. The proposed method is to derive a SDRM trace by summing up all singles from all detectors through the PET data acquisition...
January 18, 2017: Medical Physics
https://www.readbyqxmd.com/read/28097640/priming-increases-the-anti-tumor-effect-and-therapeutic-window-of-177-lu-octreotate-in-nude-mice-bearing-human-small-intestine-neuroendocrine-tumor-got1
#20
Johanna Dalmo, Johan Spetz, Mikael Montelius, Britta Langen, Yvonne Arvidsson, Henrik Johansson, Toshima Z Parris, Khalil Helou, Bo Wängberg, Ola Nilsson, Maria Ljungberg, Eva Forssell-Aronsson
BACKGROUND: (177)Lu-[DOTA(0), Tyr(3)]-octreotate ((177)Lu-octreotate) is used for treatment of patients with somatostatin receptor (SSTR) expressing neuroendocrine tumors. However, complete tumor remission is rarely seen, and optimization of treatment protocols is needed. In vitro studies have shown that irradiation can up-regulate the expression of SSTR1, 2 and 5, and increase (177)Lu-octreotate uptake. The aim of the present study was to examine the anti-tumor effect of a (177)Lu-octreotate priming dose followed 24 h later by a second injection of (177)Lu-octreotate compared to a single administration of (177)Lu-octreotate, performed on the human small intestine neuroendocrine tumor cell line, GOT1, transplanted to nude mice...
December 2017: EJNMMI Research
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