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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
https://www.readbyqxmd.com/read/28685506/update-on-modern-management-of-pheochromocytoma-and-paraganglioma
#7
REVIEW
Jacques W M Lenders, Graeme Eisenhofer
Despite all technical progress in modern diagnostic methods and treatment modalities of pheochromocytoma/paraganglioma, early consideration of the presence of these tumors remains the pivotal link towards the best possible outcome for patients. A timely diagnosis and proper treatment can prevent the wide variety of potentially catastrophic cardiovascular complications. Modern biochemical testing should include tests that offer the best available diagnostic performance, measurements of metanephrines and 3-methoxytyramine in plasma or urine...
June 2017: Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28678084/magnetic-resonance-lymphography-at-9-4-t-using-a-gadolinium-based-nanoparticle-in-rats-investigations-in-healthy-animals-and-in-a-hindlimb-lymphedema-model
#8
Andreas Müller, Peter Fries, Bijan Jelvani, François Lux, Claudia E Rübe, Stephanie Kremp, Pietro Giovanoli, Arno Buecker, Michael D Menger, Matthias W Laschke, Florian S Frueh
OBJECTIVES: Magnetic resonance lymphography (MRL) in small animals is a promising but challenging tool in preclinical lymphatic research. In this study, we compared the gadolinium (Gd)-based nanoparticle AGuIX with Gd-DOTA for interstitial MRL in healthy rats and in a chronic rat hindlimb lymphedema model. MATERIALS AND METHODS: A comparative study with AGuIX and Gd-DOTA for interstitial MRL was performed in healthy Lewis rats (n = 6). For this purpose, 75 μL of 3 mM AGuIX (containing 30 mM Gd-DOTA side residues) and 75 μL 30 mM Gd-DOTA were injected simultaneously in the right and left hindlimbs...
July 3, 2017: Investigative Radiology
https://www.readbyqxmd.com/read/28675208/novel-bifunctional-data-chelator-for-quick-access-to-site-directed-pet-68-ga-radiotracers-preclinical-proof-of-principle-with-tyr-3-octreotide
#9
Berthold A Nock, Aikaterini Kaloudi, Johannes Nagel, Jean-Philippe Sinnes, Frank Roesch, Theodosia Maina
Molecular imaging of tumors with the PET radionuclide (68)Ga has gained momentum in clinical oncology due to the expanding availability of commercial (68)Ge/(68)Ga-generators in combination with state-of-the-art PET/CT and PET/MRI hybrid imaging systems. Concurrently, interesting peptide-based or small-size vectors have been developed for theranostic use in cancer patients. Owing to the short half-life of (68)Ga (t1/2 = 67.7 min) and the sensitivity of many targeting biomolecules, labeling and kit reconstitution in mild conditions allowing for quick access to ready-for-injection PET-tracers are highly desirable...
July 4, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28670120/near-infrared-light-triggered-theranostics-for-tumor-specific-enhanced-multimodal-imaging-and-photothermal-therapy
#10
Bo Wu, Bing Wan, Shu-Ting Lu, Kai Deng, Xiao-Qi Li, Bao-Lin Wu, Yu-Shuang Li, Ru-Fang Liao, Shi-Wen Huang, Hai-Bo Xu
The major challenge in current clinic contrast agents (CAs) and chemotherapy is the poor tumor selectivity and response. Based on the self-quench property of IR820 at high concentrations, and different contrast effect ability of Gd-DOTA between inner and outer of liposome, we developed "bomb-like" light-triggered CAs (LTCAs) for enhanced CT/MRI/FI multimodal imaging, which can improve the signal-to-noise ratio of tumor tissue specifically. IR820, Iohexol and Gd-chelates were firstly encapsulated into the thermal-sensitive nanocarrier with a high concentration...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28661213/dynamic-contrast-enhanced-mri-of-the-microenvironment-of-pancreatic-adenocarcinoma-xenografts
#11
Catherine S Wegner, Anette Hauge, Jon-Vidar Gaustad, Lise Mari K Andersen, Trude G Simonsen, Kanthi Galappathi, Einar K Rofstad
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with poor outcome. Resistance to treatment is associated with impaired vascularity, extensive hypoxia, and interstitial hypertension. In this study, the potential of dynamic contrast-enhanced (DCE)-MRI as a method for assessing the microvascular density (MVD), the fraction of hypoxic tissue, and the interstitial fluid pressure (IFP) of PDACs was investigated. MATERIAL AND METHODS: Intramuscular BxPC-3, Capan-2, MIAPaCa-2, and Panc-1 PDAC xenografts were used as preclinical models of human PDACs...
June 29, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28656751/gadolinium-labeled-biodegradable-dendron-hyaluronic-acid-hybrid-and-its-subsequent-application-as-a-safe-and-efficient-magnetic-resonance-imaging-contrast-agent
#12
Chunhua Guo, Ling Sun, Hao Cai, Zhenyu Duan, Shiyong Zhang, Qiyong Gong, Kui Luo, Zhongwei Gu
Novel magnetic resonance imaging (MRI) contrast agents with high sensitivity and good biocompatibility are required for the diagnosis of cancer. Herein, we prepared and characterized the gadolinium [Gd(III)]-labeled peptide dendron-hyaluronic acid (HA) conjugate-based hybrid (dendronized-HA-DOTA-Gd) by combining the advantages of HA and the peptide dendron. The dendronized-HA-DOTA-Gd hybrid with 3.8% Gd(III) as weight percentage showed a negative zeta potential (-35 mV). The in vitro degradation results indicated that the dendronized-HA-DOTA-Gd hybrid degraded into products with low molecular weights in the presence of hyaluronidase...
July 19, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28655418/synthesis-and-characterization-of-monophosphinic-acid-dota-derivative-a-smart-tool-with-functionalities-for-multimodal-imaging
#13
Satya Narayana Murthy Chilla, Ondrej Zemek, Jan Kotek, Sébastien Boutry, Lionel Larbanoix, Coralie Sclavons, Luce Vander Elst, Ivan Lukes, Robert N Muller, Sophie Laurent
A new facile synthetic strategy was developed to prepare bifunctional monophosphinic acid Ln-DOTA derivatives, Gd-DO2AGAP(NBn) and Gd- DO2AGAP(ABn). The relaxivities of the Gd-complexes are enhanced compared to Gd-DOTA. Monophosphinic acid arm of these Gd-complexes affords enhancement of inner sphere water exchange rate due to its steric bulkiness. The different functionalities of DO2AGAP(NBn) were appended in trans positions and are designed to conjugate identical or different vectors according to the potential applications...
June 15, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28647539/chemical-addressability-of-potato-virus-x-for-its-applications-in-bio-nanotechnology
#14
Duc H T Le, He Hu, Ulrich Commandeur, Nicole F Steinmetz
Potato virus X (PVX), a type member of the plant virus potexvirus group, offers a unique nanotechnology platform based on its high aspect ratio and flexible filamentous shape. The PVX platform has already been engineered and studied for its uses in imaging, drug delivery, and immunotherapies. While genetic engineering procedures are well established for PVX, there is limited information about chemical conjugation strategies for functionalizing PVX, partly due to the lack of structural information of PVX at high resolution...
June 21, 2017: Journal of Structural Biology
https://www.readbyqxmd.com/read/28638478/-177-lu-labeled-phosphoramidate-based-psma-inhibitors-the-effect-of-an-albumin-binder-on-biodistribution-and-therapeutic-efficacy-in-prostate-tumor-bearing-mice
#15
Cindy J Choy, Xiaoxi Ling, Jonathan J Geruntho, Sophia K Beyer, Joseph D Latoche, Beatrice Langton-Webster, Carolyn J Anderson, Clifford E Berkman
Prostate-specific membrane antigen (PSMA) continues to be an active biomarker for small-molecule PSMA-targeted imaging and therapeutic agents for prostate cancer and various non-prostatic tumors that are characterized by PSMA expression on their neovasculature. One of the challenges for small-molecule PSMA inhibitors with respect to delivering therapeutic payloads is their rapid renal clearance. In order to overcome this pharmacokinetic challenge, we outfitted a (177)Lu-labeled phosphoramidate-based PSMA inhibitor (CTT1298) with an albumin-binding motif (CTT1403) and compared its in vivo performance with that of an analogous compound lacking the albumin-binding motif (CTT1401)...
2017: Theranostics
https://www.readbyqxmd.com/read/28637802/tumor-uptake-of-64-cu-dota-trastuzumab-in-patients-with-metastatic-breast-cancer
#16
Joanne E Mortimer, James R Bading, Jinha M Park, Paul H Frankel, Mary I Carroll, Tri T Tran, Erasmus K Poku, Russell C Rockne, Andrew A Raubitschek, John E Shively, David M Colcher
Purpose: To characterize the relationship between tumor uptake of (64)Cu-DOTA-trastuzumab as measured by PET/CT and standard, immunohistochemistry (IHC)-based, histopathologic classification of human epidermal growth factor receptor 2 (HER2) status in women with metastatic breast cancer (MBC). Experimental Design: Women with biopsy-confirmed MBC and not given trastuzumab for [&ge] 2 months underwent complete staging, including (18)F-fluorodeoxyglucose PET/CT. Patients were classified as HER2-positive (HER2+) or negative (HER2-) based on fluorescence in situ hybridization (FISH)-supplemented IHC of biopsied tumor tissue...
June 21, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28636973/amide-to-triazole-switch-vs-in-vivo-nep-inhibition-approaches-to-promote-radiopeptide-targeting-of-grpr-positive-tumors
#17
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
#18
Peter Niedbalski, Christopher Parish, Qing Wang, Andhika Kiswandhi, Zahra Hayati, Likai Song, Lloyd 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 (13)C polarization by a factor of 2 or 3...
June 28, 2017: Journal of Physical Chemistry. A
https://www.readbyqxmd.com/read/28628723/a-multifunctional-radiotheranostic-agent-for-dual-targeting-of-breast-cancer-cells
#19
Filipe Vultos, Célia Fernandes, Filipa Mendes, Fernanda Marques, João D G Correia, Isabel Santos, Lurdes Gano
A straightforward synthetic route for a new multifunctional 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) derivative is described. To demonstrate the versatility of this pro-chelator for the preparation of radiolabeled hybrid compounds containing two different biological targeting moieties, an antitumor agent (e.g., a DNA-intercalating agent) and an estrogen receptor (ER) ligand (e.g., LXXLL-based peptide) were regiospecifically conjugated to the DOTA derivative. The bifunctional probe was radiolabeled with the auger electron emitter indium-111, and the resulting radioconjugate was 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
#20
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
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