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https://www.readbyqxmd.com/read/28813596/molecular-imaging-of-p-glycoprotein-in-chemoresistant-tumors-using-a-dual-modality-pet-fluorescence-probe
#1
Mengzhe Wang, Chengqiong Mao, Hui Wang, Xueying Ling, Zhanhong Wu, Zi-Bo Li, Xin Ming
Overexpression of P-glycoprotein (Pgp) has been considered a primary cause for multidrug resistance in a variety of cancers for three decades. However, clinical translation of Pgp targeted therapeutics has been hindered by lack of patient preselection based on the Pgp presence in tumors. We aim to develop a molecularly targeted probe for imaging tumoral Pgp in vivo with positron emission tomography (PET) and fluorescence, and to provide a tool for preselecting the patients with tumoral Pgp expression. Thus, a Pgp monoclonal antibody 15D3 was chemically modified with IRDye800 (IR800) and DOTA chelator...
August 16, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28775205/therapy-related-hematological-malignancies-after-peptide-receptor-radionuclide-therapy-with-177-lu-dota-octreotate-incidence-course-predicting-factors-in-patients-with-gep-nets
#2
Hendrik Bergsma, Kirsten van Lom, Mark Konijnenberg, Boen Kam, Jaap Teunissen, Wouter de Herder, Eric Krenning, Dik Kwekkeboom
Peptide Receptor Radionuclide Therapy (PRRT) may induce long-term toxicity to the bone marrow (BM). The aim of this study was to analyze persistent dysfunction of the hematopoietic system after PRRT with (177)Lu-DOTATATE in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Methods: The incidence and course of persistent hematological dysfunction (PHD) was analyzed in 274 (=GEP-NET) out of 367 patients with somatostatin receptor-positive tumors. PHD was defined as diagnosis of Myelodysplastic Syndrome (MDS), Acute Myeloid Leukemia (AML), Myeloproliferative Neoplasms (MPN), Myelodysplastic/Myeloproliferative neoplasms (MDS/MPN) or otherwise unexplained cytopenia (for more than 6 months)...
August 3, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28771849/in-vivo-evaluation-of-an-engineered-cyclotide-as-specific-cxcr4-imaging-reagent
#3
Wojciech G Lesniak, Teshome Aboye, Samit Chatterjee, Julio A Camarero, Sridhar Nimmagadda
The CXCR4 chemokine receptor plays a key regulatory role in many biological functions, including embryonic development and controlling leukocyte functions during inflammation and immunity. CXCR4 has been also associated with multiple types of cancers where its overexpression/activation promotes metastasis, angiogenesis, and tumor growth and/or survival. Furthermore, CXCR4 is involved in HIV replication, as it is a co-receptor for viral entry into host cells. Altogether, these features make CXCR4 a very attractive target for the development of imaging and therapeutic agents...
August 3, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28770275/visualization-of-her2-specific-breast-cancer-intratumoral-heterogeneity-using-64-cu-dota-trastuzumab-pet
#4
Shinsuke Sasada, Hiroaki Kurihara, Takayuki Kinoshita, Masayuki Yoshida, Natsuki Honda, Tatsunori Shimoi, Akihiko Shimomura, Kan Yonemori, Chikako Shimizu, Akinobu Hamada, Yousuke Kanayama, Yasuyoshi Watanabe, Yasuhiro Fujiwara, Kenji Tamura
No abstract text is available yet for this article.
August 3, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28765924/mri-reveals-slow-clearance-of-dead-cell-transplants-in-mouse-forelimb-muscles
#5
Yanhui Zhang, Hongyan Zhang, Lijun Ding, Hailu Zhang, Pengli Zhang, Haizhen Jiang, Bo Tan, Zongwu Deng
A small molecule tetraazacyclododecane-1,4,7,10-tetraacetic acid (Gd‑DOTA)4‑TPP agent is used to label human mesenchymal stem cells (hMSCs) via electroporation (EP). The present study assessed the cytotoxicity of cell labeling, in addition to its effect on cell differentiation potential. There were no significant adverse effects on cell viability or differentiation induced by either EP or cellular uptake of (Gd‑DOTA)4‑TPP. Labeled live and dead hMSCs were transplanted into mouse forelimb muscles. T2‑weighted magnetic resonance imaging (MRI) was used to track the in vivo fate of the cell transplants...
July 27, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28758669/dota-analogues-with-a-phosphinate-iminodiacetate-pendant-arm-modification-of-the-complex-formation-rate-with-a-strongly-chelating-pendant
#6
Soňa Procházková, Vojtěch Kubíček, Zuzana Böhmová, Kateřina Holá, Jan Kotek, Petr Hermann
The new ligand H6do3aP(ida) combines the macrocyclic DOTA-like cavity and the open-chain iminodiacetate group connected through a coordinating phosphinate spacer. Its acid-base and coordination properties in solution were studied by potentiometry. Thermodynamic coordination characteristics of both chelating units are similar to those reported for H4dota and iminodiacetic acid themselves, respectively, so, macrocyclic and iminodiacetate units behave independently. The formation kinetics of the Ce(iii)-H6do3aP(ida) complex was studied by UV-Vis spectrophotometry...
July 31, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28748183/neodymium-140-dota-lm3-evaluation-of-an-in-vivo-generator-for-pet-with-a-non-internalizing-vector
#7
Gregory W Severin, Lotte K Kristensen, Carsten H Nielsen, Jesper Fonslet, Andreas I Jensen, Anders F Frellsen, K M Jensen, Dennis R Elema, Helmut Maecke, Andreas Kjær, Karl Johnston, Ulli Köster
(140)Nd (t1/2 = 3.4 days), owing to its short-lived positron emitting daughter (140)Pr (t1/2 = 3.4 min), has promise as an in vivo generator for positron emission tomography (PET). However, the electron capture decay of (140)Nd is chemically disruptive to macrocycle-based radiolabeling, meaning that an in vivo redistribution of the daughter (140)Pr is expected before positron emission. The purpose of this study was to determine how the delayed positron from the de-labeled (140)Pr affects preclinical imaging with (140)Nd...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28745238/effect-of-number-of-bifunctional-chelating-agents-on-the-pharmacokinetics-and-immunoreactivity-of-177lu-labeled-rituximab-a-systemic-study
#8
Mohini Guleria, Tapas Das, Chandan Kumar, Rohit Sharma, Jeyachitra Amirdhanayagam, Haladhar D Sarma, Ashutosh Dash
OBJECTIVE: Monoclonal antibodies (mAbs) have been radiolabeled with a variety of radioisotopes utilizing various kinds of bi-functional chelating agents (BFCAs) with an aim to develop suitable agents for radioimmunotherapy. The number of BFCA moieties present per antibody molecule plays a significant role in determining the pharmacokinetics and immunoreactivity exhibited by the radiolabeled antibodies. The objective of the present study is to evaluate the effect of number of BFCA moieties present per antibody molecule on the pharmacokinetics and immunoreactivity of the 177Lu-labeled Rituximab...
July 25, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28745059/near-infrared-neodymium-tag-for-quantifying-targeted-biomarker-and-counting-its-host-circulating-tumor-cells
#9
Chunlan Liu, Shu Lu, Limin Yang, Peijie Chen, Peiming Bai, Qiuquan Wang
Quantitative information on a targeted analyte in a complex biological system is the most basic premise for understanding its involved mechanisms, and thus precise diagnosis of a disease if it is a so-called biomarker. Here, we designed and synthesized a neodymium (Nd)-cored tag [1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid (DOTA)-Nd complex together with a light-harvesting antenna aminofluorescein (AMF, λex/em = 494/520 nm), AMF-DOTA-Nd] with duplex signals, second near-infrared (NIR) window luminescence (λem = 1065 nm, 2...
August 9, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28740605/synthesis-of-a-fluorescently-labeled-68-ga-dota-toc-analog-for-somatostatin-receptor-targeting
#10
Sukhen C Ghosh, Servando Hernandez Vargas, Melissa Rodriguez, Susanne Kossatz, Julie Voss, Kendra S Carmon, Thomas Reiner, Agnes Schonbrunn, Ali Azhdarinia
Fluorescently labeled imaging agents can identify surgical margins in real-time to help achieve complete resections and minimize the likelihood of local recurrence. However, photon attenuation limits fluorescence-based imaging to superficial lesions or lesions that are a few millimeters beneath the tissue surface. Contrast agents that are dual-labeled with a radionuclide and fluorescent dye can overcome this limitation and combine quantitative, whole-body nuclear imaging with intraoperative fluorescence imaging...
July 13, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28732021/in-vitro-comparison-of-213bi-and-177lu-radiation-for-peptide-receptor-radionuclide-therapy
#11
Ho Sze Chan, Erik de Blois, Alfred Morgenstern, Frank Bruchertseifer, Marion de Jong, Wouter Breeman, Mark Konijnenberg
BACKGROUND: Absorbed doses for α-emitters are different from those for β-emitters, as the high linear energy transfer (LET) nature of α-particles results in a very dense energy deposition over a relatively short path length near the point of emission. This highly localized and therefore high energy deposition can lead to enhanced cell-killing effects at absorbed doses that are non-lethal in low-LET type of exposure. Affinities of DOTA-DPhe1-Tyr3-octreotate (DOTATATE), 115In-DOTATATE, 175Lu-DOTATATE and 209Bi-DOTATATE were determined in the K562-SST2 cell line...
2017: PloS One
https://www.readbyqxmd.com/read/28730467/organ-retention-of-gadolinium-in-mother-and-pup-mice-effect-of-pregnancy-and-type-of-gadolinium-based-contrast-agents
#12
Khongorzul Erdene, Takahito Nakajima, Satomi Kameo, Miski Aghnia Khairinisa, Oyunbold Lamid-Ochir, Amartuvshin Tumenjargal, Noriyuki Koibuchi, Hiroshi Koyama, Yoshito Tsushima
PURPOSE: To investigate the effect of pregnancy and type of gadolinium (Gd)-based contrast agents (GBCAs) on organ retention of Gd in mother and pup mice after maternal administration. MATERIALS AND METHODS: Gd-DTPA-BMA (gadodiamide) or Gd-DOTA (gadoterate dimeglumine) was administered (2.0 mmol/kg of maternal weight) four times to pregnant Balb/c mice from gestational day 16-19, respectively. At 28 days after birth, they were euthanized and their organs (blood, brain, liver, kidney, spleen, and bone) were removed for the measurement of Gd by inductively coupled plasma mass spectrometry...
July 20, 2017: Japanese Journal of Radiology
https://www.readbyqxmd.com/read/28729680/the-use-of-radiocobalt-as-a-label-improves-imaging-of-egfr-using-dota-conjugated-affibody-molecule
#13
Javad Garousi, Ken G Andersson, Johan H Dam, Birgitte B Olsen, Bogdan Mitran, Anna Orlova, Jos Buijs, Stefan Ståhl, John Löfblom, Helge Thisgaard, Vladimir Tolmachev
Several anti-cancer therapies target the epidermal growth factor receptor (EGFR). Radionuclide imaging of EGFR expression in tumours may aid in selection of optimal cancer therapy. The (111)In-labelled DOTA-conjugated ZEGFR:2377 Affibody molecule was successfully used for imaging of EGFR-expressing xenografts in mice. An optimal combination of radionuclide, chelator and targeting protein may further improve the contrast of radionuclide imaging. The aim of this study was to evaluate the targeting properties of radiocobalt-labelled DOTA-ZEGFR:2377...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28728415/-177-lu-labeled-cyclic-minigastrin-analogues-with-therapeutic-activity-in-cck2r-expressing-tumors-preclinical-evaluation-of-a-kit-formulation
#14
Christine Rangger, Maximilian Klingler, Lajos Balogh, Zita Pöstényi, Andras Polyak, Dariusz Pawlak, Renata Mikołajczak, Elisabeth von Guggenberg
Minigastrin (MG) analogues specifically target cholecystokinin-2 receptors (CCK2R) expressed in different tumors and enable targeted radiotherapy of advanced and disseminated disease when radiolabeled with a beta emitter such as (177)Lu. Especially truncated MG analogues missing the penta-Glu sequence are associated with low kidney retention and seem therefore most promising for therapeutic use. Based on [d-Glu(1),desGlu(2-6)]MG (MG11) we have designed the two cyclic MG analogues cyclo(1,9)[γ-d-Glu(1),desGlu(2-6),d-Lys(9)]MG (cyclo-MG1) and cyclo(1,9)[γ-d-Glu(1),desGlu(2-6),d-Lys(9),Nle(11)]MG (cyclo-MG2)...
August 7, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28721684/pharmacokinetics-microscale-distribution-and-dosimetry-of-alpha-emitter-labeled-anti-pd-l1-antibodies-in-an-immune-competent-transgenic-breast-cancer-model
#15
Jessie R Nedrow, Anders Josefsson, Sunju Park, Tom Bäck, Robert F Hobbs, Cory Brayton, Frank Bruchertseifer, Alfred Morgenstern, George Sgouros
BACKGROUND: Studies combining immune checkpoint inhibitors with external beam radiation have shown a therapeutic advantage over each modality alone. The purpose of these works is to evaluate the potential of targeted delivery of high LET radiation to the tumor microenvironment via an immune checkpoint inhibitor. METHODS: The impact of protein concentration on the distribution of (111)In-DTPA-anti-PD-L1-BC, an (111)In-antibody conjugate targeted to PD-L1, was evaluated in an immunocompetent mouse model of breast cancer...
December 2017: EJNMMI Research
https://www.readbyqxmd.com/read/28711759/dft-study-of-the-interaction-between-dota-chelator-and-competitive-alkali-metal-ions
#16
E Frimpong, A A Skelton, B Honarparvar
1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetracetic acid (DOTA) is an important chelator for radiolabeling of pharmaceuticals. The ability of alkali metals found in the body to complex with DOTA and compete with radio metal ions can alter the radiolabeling process. Non-covalent interactions between DOTA complexed with alkali metals Li(+), Na(+), K(+) and Rb(+), are investigated with density functional theory using B3LYP and ωB97XD functionals. Conformational possibilities of DOTA were explored with a varying number of carboxylic pendant arms of DOTA in close proximity to the ions...
June 29, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28705917/curative-multi-cycle-radioimmunotherapy-monitored-by-quantitative-spect-ct-based-theranostics-using-bispecific-antibody-pretargeting-strategy-in-colorectal-cancer
#17
Sarah M Cheal, Edward K Fung, Miteshkumar V Patel, Blesida Punzalan, Hong Xu, Hong-Fen Guo, Pat B Zanzonico, Sebastien Monette, Karl Dane Wittrup, Nai-Kong Cheung, Steven M Larson
Radioimmunotherapy of solid tumors using antibody-targeted radionuclides has been limited by low therapeutic indices (TI). We recently reported a novel three-step pretargeted radioimmunotherapy (PRIT) strategy based on a glycoprotein A33 (GPA33)-targeting bispecific antibody (bsAb) and a small-molecule radioactive hapten, a complex of lutetium-177 ((177)Lu) and S-2-(4-aminobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid ((177)Lu-DOTA-Bn) that leads to high TIs for radiosensitive tissues such as blood (TI = 73) and kidney (TI = 12)...
July 13, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28702554/in-vitro-and-in-vivo-trackable-titanocene-based-complexes-using-optical-imaging-or-spect
#18
Océane Florès, Audrey Trommenschlager, Souheila Amor, Fernanda Marques, Francisco Silva, Lurdes Gano, Franck Denat, Maria Paula Cabral Campello, Christine Goze, Ewen Bodio, Pierre Le Gendre
A novel Ti/(111)In-heterometallic radiotheranostic along with non-radioactive Ti/In, Ti/Lu, and Ti/Y analogues has been reported, thanks to the design of a challenging synthesis of the first titanocene-DOTA ligand. The corresponding titanocene-BODIPY complex was developed for in vitro tracking by optical imaging. The different complexes were characterized and their antiproliferative properties were evaluated on three cancer cell lines (A2780, B16F1, and PC3). As a proof of concept, initial studies in healthy mice were performed with a Ti/(111)In derivative to obtain information about its uptake, its biodistribution, and its excretion...
July 12, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28689221/variable-refocusing-flip-angle-single-shot-fast-spin-echo-imaging-of-liver-lesions-increased-speed-and-lesion-contrast
#19
Robert M Hicks, Andreas M Loening, Michael A Ohliger, Shreyas S Vasanawala, Thomas A Hope
PURPOSE: To evaluate acquisition time and clinical image quality of a variable refocusing flip angle (vrf) single-shot fast spin echo (SSFSE) sequence in comparison with a conventional SSFSE sequence for imaging of liver lesions in patients undergoing whole-body PET/MRI for oncologic staging. METHODS: A vrfSSFSE sequence was acquired in 43 patients with known pancreatic neuroendocrine tumors undergoing (68)Ga-DOTA-TOC PET on a simultaneous time-of-flight 3.0T PET/MRI...
July 8, 2017: Abdominal Radiology
https://www.readbyqxmd.com/read/28686796/quesp-and-quest-revisited-fast-and-accurate-quantitative-cest-experiments
#20
Moritz Zaiss, Goran Angelovski, Eleni Demetriou, Michael T McMahon, Xavier Golay, Klaus Scheffler
PURPOSE: Chemical exchange saturation transfer (CEST) NMR or MRI experiments allow detection of low concentrated molecules with enhanced sensitivity via their proton exchange with the abundant water pool. Be it endogenous metabolites or exogenous contrast agents, an exact quantification of the actual exchange rate is required to design optimal pulse sequences and/or specific sensitive agents. METHODS: Refined analytical expressions allow deeper insight and improvement of accuracy for common quantification techniques...
July 7, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
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