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https://www.readbyqxmd.com/read/28184015/dual-pi3k-mtor-inhibition-in-colorectal-cancers-with-apc-and-pik3ca-mutations
#1
Tyler M Foley, Susan N Payne, Cheri A Pasch, Alex E Yueh, Dana R Van De Hey, Demetra P Korkos, Linda Clipson, Molly E Maher, Kristina A Matkowskyj, Michael A Newton, Dustin A Deming
Therapeutic targeting of the PI3K pathway is an active area of research in multiple cancer types, including breast and endometrial cancers. This pathway is commonly altered in cancer and plays an integral role in numerous vital cellular functions. Mutations in the PIK3CA gene, resulting in a constitutively active form of PI3K, often occur in colorectal cancer, though the population of patients who would benefit from targeting this pathway has yet to be identified. In human colorectal cancers, PIK3CA mutations most commonly occur concomitantly with loss of adenomatous polyposis coli (APC)...
9, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28179292/effect-of-androgen-on-normal-biodistribution-of-18-f-2-fluoro-5-methyl-1-beta-d-arabinofuranosyluracil-18f-fmau-in-athymic-non-tumor-bearing-male-mice
#2
Hossein Jadvar, Ryan Park, Li-Peng Yap, Kai Chen, Lindsey Hughes, Peter Conti
AIM: We assessed the association between the presence and absence of androgen on the normal biodistribution of the positron emission tomography (PET) cellular proliferation imaging biomarker, [(18)F]-2'-Fluoro-5-methyl-1-beta-D-arabinofuranosyluracil ((18)F-FMAU), in mice. MATERIALS AND METHODS: Non-castrated (n=4) and castrated (n=4) athymic non-tumor-bearing male mice served as models for presence and absence, respectively, of androgen. MicroPET-CT scans were performed 1 h following tail vein administration of 200 uCi of (18)F-FMAU...
2017: Anticancer Research
https://www.readbyqxmd.com/read/28159919/evaluation-of-radiofluorinated-carboximidamides-as-potential-ido-targeted-pet-tracers-for-cancer-imaging
#3
Xuan Huang, Zhongjie Pan, Michael L Doligalski, Xia Xiao, Epifanio Ruiz, Mikalai M Budzevich, Haibin Tian
IDO1 is an enzyme catalyzing the initial and rate-limiting step in the catabolism of tryptophan along the kynurenine pathway. IDO1 expression could suppress immune responses by blocking T-lymphocyte proliferation locally, suggesting a role of IDO in the regulation of immune responses. The goal of this study was to evaluate the potential of radiofluorinated carboximidamides as selective PET radioligands for IDO1. Specific binding correlated with IDO1 expression as measured through in vitro, microPET experiments...
January 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28157626/evaluation-of-18-f-atri-as-pet-tracer-for-in-vivo-imaging-of-atr-in-mouse-models-of-brain-cancer
#4
Giuseppe Carlucci, Brandon Carney, Ahmad Sadique, Axel Vansteene, Jun Tang, Thomas Reiner
RATIONALE: Ataxia telangiectasia and Rad3-related (ATR) threonine serine kinase is one of the key elements in orchestrating the DNA damage response (DDR). As such, inhibition of ATR can amplify the effects of chemo- and radiation-therapy, and several ATR inhibitors (ATRi) have already undergone clinical testing in cancer. For more accurate patient selection, monitoring and staging, real-time in vivo imaging of ATR could be invaluable; the development of appropriate imaging agents has remained a major challenge...
January 16, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28129990/chiral-resolution-of-serial-potent-and-selective-%C3%AF-1-ligands-and-biological-evaluation-of-18-f-tz3108-in-rodent-and-the-nonhuman-primate-brain
#5
Xuyi Yue, Hongjun Jin, Zonghua Luo, Hui Liu, Xiang Zhang, Ethan D McSpadden, Linlin Tian, Hubert P Flores, Joel S Perlmutter, Stanley M Parsons, Zhude Tu
Twelve optically pure enantiomers were obtained using either crystallization or chiral high performance liquid chromatography (HPLC) separation methodologies to resolve six racemic sigma-1 (σ1) receptor ligands. The in vitro binding affinities of each enantiomer for σ1, σ2 receptors and vesicular acetylcholine transporter (VAChT) were determined. Out of the 12 optically pure enantiomers, five displayed very high affinities for σ1 (Ki<2nM) and high selectivity for σ1 versus σ2 and VAChT (>100-fold)...
February 15, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28119212/preparation-and-68-ga-radiolabeling-of-porous-zirconia-nanoparticle-platform-for-pet-ct-imaging-guided-drug-delivery
#6
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/28094184/in-vivo-evaluation-of-igf1r-ir-pet-ligand-18-f-bms-754807-in-rodents
#7
Jaya Prabhakaran, Stephen L Dewey, Richard McClure, Norman R Simpson, Mohammed N Tantawy, J John Mann, Wellington Pham, J S Dileep Kumar
In vivo evaluation of [(18)F]BMS-754807 binding in mice and rats using microPET and biodistribution methods is described herein. The radioligand shows consistent binding characteristics, in vivo, in both species. Early time frames of the microPET images and time activity curves of brain indicate poor penetration of the tracer across the blood brain barrier (BBB) in both species. However, microPET experiments in mice and rats show high binding of the radioligand outside the brain to heart, pancreas and muscle, the organs known for higher expression of IGF1R/1R...
January 7, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28078167/a-novel-strategy-for-attenuating-opioid-withdrawal-in-neonates
#8
Giovanni C Santoro, Samarth Shukla, Krishna Patel, Jakub Kaczmarzyk, Stergiani Agorastos, Sandra Scherrer, Yoon Young Choi, Christina Veith, Joseph Carrion, Rebecca Silverman, Danielle Mullin, Mohamed Ahmed, Wynne K Schiffer, Jonathan D Brodie, Stephen L Dewey
The rate of Neonatal Abstinence Syndrome (NAS) has drastically increased over the past decade. The average hospital expense per NAS patient has tripled, while the number of babies born to opioid-dependent mothers has increased to 5 in 1000 births. Current treatment options are limited to opioid replacement and tapering. Consequently, we examined the efficacy of prenatal, low-dose and short-term vigabatrin (γ-vinyl GABA, GVG) exposure for attenuating these symptoms as well as the metabolic changes observed in the brains of these animals upon reaching adolescence...
August 2016: Journal of Addiction Research & Therapy
https://www.readbyqxmd.com/read/28052582/magnetically-driven-nanoparticles-18-fdg-radiolabelling-and-positron-emission-tomography-biodistribution-study
#9
Mariarosaria De Simone, Daniele Panetta, Emilia Bramanti, Cristiana Giordano, Maria C Salvatici, Lisa Gherardini, Arianna Menciassi, Silvia Burchielli, Caterina Cinti, Piero A Salvadori
Superparamagnetic iron oxide nanoparticles (SPIONs) have received increasing interest as contrast media in biomedical imaging and innovative therapeutic tools, in particular for loco-regional ablative treatments and drug delivery. The future of therapeutic applications would strongly benefit from improving the capability of the nanostructured constructs to reach the selected target, in particular beyond the intravascular space. Besides the decoration of SPIONs surface with ad hoc bioactive molecules, external magnetic fields are in principle able to remotely influence SPIONs' physiological biodistribution and concentrate them to a specific anatomical region or portion of a tissue...
November 2016: Contrast Media & Molecular Imaging
https://www.readbyqxmd.com/read/28049295/-64-cu-labeled-trastuzumab-fab-peg24-egf-radioimmunoconjugates-bispecific-for-her2-and-egfr-pharmacokinetics-biodistribution-and-tumor-imaging-by-pet-in-comparison-to-monospecific-agents
#10
Luke Yongkyu Kwon, Deborah A Scollard, Raymond M Reilly
Heterodimerization of EGFR with HER2 coexpressed in breast cancer (BC) promotes tumor growth, and increased EGFR expression is associated with trastuzumab resistance. Our aim was to construct (64)Cu-labeled bispecific radioimmunoconjugates (bsRIC) composed of trastuzumab Fab, which binds HER2 linked through a polyethylene glycol (PEG24) spacer to EGF, and to compare their pharmacokinetic, biodistribution, and tumor imaging characteristics by positron-emission tomography (PET). bsRICs were generated by linking maleimide modified trastuzumab Fab with thiolated EGF through a thioether bond...
January 18, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28048625/tu-h-206-02-novel-linearly-filled-derenzo-pet-phantom-design
#11
S Graves, B Cox, M Farhoud, H Valdovinos, J Jeffery, K Eliceiri, T Barnhart, R Nickles
PURPOSE: To design a linearly-filled Derenzo positron emission tomography (PET) phantom, eliminating the extraneous radioisotope volumes in a conventional reservoir-type design. This activity reduction combined with the elimination of bubbles in smaller phantom channels would significantly reduce personnel dose, radioisotope cost, and would improve image quality by reducing out-of-slice activity scatter. METHODS: A computer-aided design (CAD) was created of a modular Derenzo phantom consisting of three phantom layers with gaskets between the layers...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28031412/dual-pi3k-mtor-inhibition-in-colorectal-cancers-with-apc-and-pik3ca-mutations
#12
Tyler M Foley, Susan N Payne, Cheri A Pasch, Alex E Yueh, Dana R Van De Hey, Demetra P Korkos, Linda Clipson, Molly E Maher, Kristina A Matkowskyj, Michael A Newton, Dustin A Deming
: Therapeutic targeting of the phosphoinositide 3-kinase (PI3K) pathway is an active area of research in multiple cancer types, including breast and endometrial cancers. This pathway is commonly altered in cancer and plays an integral role in numerous vital cellular functions. Mutations in the PIK3CA gene, resulting in a constitutively active form of PI3K, often occur in colorectal cancer (CRC), though the population of patients who would benefit from targeting this pathway has yet to be identified...
December 28, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28009175/carbon-11-and-fluorine-18-radiolabeled-pyridopyrazinone-derivatives-for-positron-emission-tomography-pet-imaging-of-phosphodiesterase-5-pde5
#13
Rufael Chekol, Olivier Gheysens, Muneer Ahamed, Jan Cleynhens, Peter Pokreisz, Greet Vanhoof, Stefan Janssens, Alfons Verbruggen, Guy Bormans
The cyclic guanosine monophosphate (cGMP) specific phosphodiesterase type 5 (PDE5) plays an important role in various pathologies including pulmonary arterial hypertension and cardiomyopathy. PDE5 represents an important therapeutic and/or prognostic target, but noninvasive assessment of PDE5 expression is lacking. The purpose of this study was to develop and evaluate pyridopyrazinone derivatives labeled with carbon-11 or fluorine-18 as PDE5-specific PET tracers. In biodistribution studies, highest PDE5-specific retention was observed for [(11)C]-12 and [(18)F]-17 in the lungs of wild-type mice and in the myocardium of transgenic mice with cardiomyocyte-specific PDE5 overexpression at 30 min postinjection...
December 23, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27980051/4-11c-methoxy-n-2-diethylaminoethyl-benzamide-a-novel-probe-to-selectively-target-melanoma
#14
Pradeep K Garg, Rachid Nazih, Yanjun Wu, Ravi A Singh, Sudha Garg
: We report the synthesis and preclinical evaluation of (11)C-labeled novel probe to target melanoma using Positron Emission Tomography (PET). METHODS: The target compound 4-(11)-Cmethoxy N-(2-diethylaminoethyl) benzamide (4-(11)C-MBZA) was prepared via the (11)C-methylation of 4-hydroxy N-(2-diethylaminoethyl) benzamide (4-HBZA). The in vitro binding was performed using B16F1 (Melanoma cells), MCF-10A (breast epithelial cells) and MDA-MB 231 (breast cancer cells)...
December 15, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/27980048/influence-of-animal-heating-on-pet-imaging-quantification-and-kinetics-results-on-the-biodistribution-of-18f-tetrafluoroborate-and-18f-fdg-in-mice
#15
Christian Goetz, Matthias Podein, Friederike Braun, Wolfgang A Weber, Philippe Choquet, André Constantinesco, Michael Mix
: Varying environmental conditions under anesthesia may lead to unstable homeostatic conditions in rodents and thus alter kinetics. This study evaluated the impact of varying heating conditions on PET imaging quantification. METHODS: Two groups of six adult female balb-c nude mice with subcutaneously implanted tumors underwent microPET imaging after injection of (18)F-tetrafluoroborate and (18)F-fluordeoxyglucose respectively. Dynamic scans were acquired under optimal and sub-optimal heating conditions...
December 15, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/27965305/bone-marrow-cell-trafficking-analyzed-by-89zr-oxine-positron-emission-tomography-in-a-murine-transplantation-model
#16
Kingsley O Asiedu, Sho Koyasu, Lawrence P Szajek, Peter L Choyke, Noriko Sato
PURPOSE: The success of hematopoietic stem cell transplantation (HSCT) depends on donor cell homing to the bone marrow (BM). However, there is no reliable method of noninvasively monitoring the kinetics and distribution of transferred cells. Using Zirconium-89 ((89)Zr)-oxine cell labeling combined with positron emission tomography (PET) imaging, we sought to visualize and quantify donor cell homing in a mouse BM transplantation model. EXPERIMENTAL DESIGN: The effect of (89)Zr-oxine labeling on BM cell viability and differentiation was evaluated in vitro...
December 13, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27933958/-18-f-labeled-benzyldiamine-derivatives-as-novel-flexible-probes-for-positron-emission-tomography-of-cerebral-%C3%AE-amyloid-plaques
#17
Zijing Li, Xuran Zhang, Xiaoyang Zhang, Mengchao Cui, Jie Lu, Xiaodong Pan, Xianzhong Zhang
Early noninvasive visualization of cerebral β-amyloid (Aβ) plaques with positron emission tomography (PET) is the most feasible way to diagnose Alzheimer's disease (AD). In this study, a series of flexible benzyldiamine derivatives (BDA) were proposed for binding to aggregated β-amyloid 1-42 (Aβ1-42) with high adaptability, high binding affinity (6.8 ± 0.6 nM), and rapid body excretion. The methylthio (12) and ethoxyl (10) derivatives were further labeled with (18)F directly on their benzene ring and examined as PET probes for Aβ plaque imaging...
December 8, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27920093/metformin-reduces-glycometabolism-of-papillary-thyroid-carcinoma-in-vitro-and-in-vivo
#18
Chen-Tian Shen, Wei-Jun Wei, Zhong-Ling Qiu, Hong-Jun Song, Xin-Yun Zhang, Zhen-Kui Sun, Quan-Yong Luo
More aggressive thyroid cancer cells show a higher activity of glycometabolism. Targeting cancer cell metabolism has emerged as a novel approach to prevent or treat malignant tumors. Glucose metabolism regulation effect of metformin in papillary thyroid cancer was investigated in the current study. Human papillary thyroid carcinoma (PTC) cell lines BCPAP and KTC1 were used. Cell viability was detected by CCK8 assay. Glucose uptake and relative gene expression were measured in metformin (0-10 mM for 48 h)-treated cells by (18)F-FDG uptake assay and western blotting analysis, respectively...
January 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/27903730/network-patterns-associated-with-navigation-behaviors-are-altered-in-aged-nonhuman-primates
#19
James R Engle, Christopher J Machado, Michele R Permenter, Julie A Vogt, Andrew P Maurer, Alicia M Bulleri, Carol A Barnes
: The ability to navigate through space involves complex interactions between multiple brain systems. Although it is clear that spatial navigation is impaired during aging, the networks responsible for these altered behaviors are not well understood. Here, we used a within-subject design and [(18)F]FDG-microPET to capture whole-brain activation patterns in four distinct spatial behaviors from young and aged rhesus macaques: constrained space (CAGE), head-restrained passive locomotion (CHAIR), constrained locomotion in space (TREADMILL), and unconstrained locomotion (WALK)...
November 30, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27875800/evaluation-of-tspo-pet-imaging-a-marker-of-glial-activation-to-study-the-neuroimmune-footprints-of-morphine-exposure-and-withdrawal
#20
Sylvain Auvity, Sébastien Goutal, Benoît Thézé, Catarina Chaves, Benoît Hosten, Bertrand Kuhnast, Wadad Saba, Raphaël Boisgard, Irène Buvat, Salvatore Cisternino, Nicolas Tournier
INTRODUCTION: A growing area of research suggests that neuroimmunity may impact the pharmacology of opioids. Microglia is a key component of the brain immunity. Preclinical and clinical studies have demonstrated that microglial modulators may improve morphine-induced analgesia and prevent the development of tolerance and dependence. Positron emission tomography (PET) using translocator protein 18kDa (TSPO) radioligand is a clinically validated strategy for the non-invasive detection of microglial activation...
January 1, 2017: Drug and Alcohol Dependence
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