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Molecular Imaging

Timothy R DeGrado, Bradley J Kemp, Mukesh K Pandey, Huailei Jiang, Tina M Gunderson, Logan R Linscheid, Allison R Woodwick, Daniel M McConnell, Joel G Fletcher, Geoffrey B Johnson, Ronald C Petersen, David S Knopman, Val J Lowe
Abnormalities in zinc homeostasis are indicated in many human diseases, including Alzheimer disease (AD). (63)Zn-zinc citrate was developed as a positron emission tomography (PET) imaging probe of zinc transport and used in a first-in-human study in 6 healthy elderly individuals and 6 patients with clinically confirmed AD. Dynamic PET imaging of the brain was performed for 30 minutes following intravenous administration of (63)Zn-zinc citrate (∼330 MBq). Subsequently, body PET images were acquired. Urine and venous blood were analyzed to give information on urinary excretion and pharmacokinetics...
2016: Molecular Imaging
Pu Zhang, Zhide Guo, Deliang Zhang, Chang Liu, Guibing Chen, Rongqiang Zhuang, Manli Song, Hua Wu, Xianzhong Zhang
The aim of this study is to develop a copolymer-based single-photon emission computed tomography/magnetic resonance (SPECT/MR) dual-modality imaging agent that can be labeled with both technetium-99m ((99m)Tc) and gadolinium (Gd) and target asialoglycoprotein receptor (ASGPR) via galactose. Monomers of N-p-vinylbenzyl-6-(2-(4-dimethylamino)benzaldehydehydrazono) nicotinate (VNI) for labeling of (99m)Tc, 5,8-bis(carboxymethyl)-3-oxo-11-(2-oxo-2-((4-vinylbenzyl)amino)ethyl)-1-(4-vinylphenzyl)-2,5,8,11-tetraazatridecan-13-oic acid (V2DTPA) for labeling of Gd, and vinylbenzyl-O-β-d-galactopyranosyl-d-gluconamide (VLA) for targeting ASGPR were synthesized, respectively...
2016: Molecular Imaging
Benjamin H Rotstein, Michael S Placzek, Hema S Krishnan, Aleksandra Pekošak, Thomas Lee Collier, Changning Wang, Steven H Liang, Ethan S Burstein, Jacob M Hooker, Neil Vasdev
Activation of retinoid X receptors (RXRs) has been proposed as a therapeutic mechanism for the treatment of neurodegeneration, including Alzheimer's and Parkinson's diseases. We previously reported radiolabeling of a Food and Drug Administration-approved RXR agonist, bexarotene, by copper-mediated [(11)C]CO2 fixation and preliminary positron emission tomography (PET) neuroimaging that demonstrated brain permeability in nonhuman primate with regional binding distribution consistent with RXRs. In this study, the brain uptake and saturability of [(11)C]bexarotene were studied in rats and nonhuman primates by PET imaging under baseline and greater target occupancy conditions...
2016: Molecular Imaging
Fook T Lee, Ingrid J G Burvenich, Nancy Guo, Pece Kocovski, Henri Tochon-Danguy, Uwe Ackermann, Graeme J O'Keefe, Sylvia Gong, Angela Rigopoulos, Zhanqi Liu, Hui K Gan, Andrew M Scott
PURPOSE: The aims of the study were to develop and evaluate a novel residualizing peptide for labeling internalizing antibodies with (124)I to support clinical development using immuno-positron emission tomography (PET). METHODS: The anti-epidermal growth factor receptor antibody ch806 was radiolabeled directly or indirectly with isotopes and various residualizing peptides. Azido-derivatized radiolabeled peptides were conjugated to dibenzylcyclooctyne-derivatized ch806 antibody via click chemistry...
2016: Molecular Imaging
Yu Ouyang, Tae Jin Kim, Guillem Pratx
A recent method based on positron emission was reported for tracking moving point sources using the Inveon PET system. However, the effect of scanner background noise was not further explored. Here, we evaluate tracking with the Genisys4, a bismuth germanate-based PET system, which has no significant intrinsic background and may be better suited to tracking lower and/or faster activity sources. Position-dependent sensitivity of the Genisys4 was simulated in Geant4 Application for Tomographic Emission (GATE) using a static (18)F point source...
2016: Molecular Imaging
Anthony R Guastella, Sharon K Michelhaugh, Neil V Klinger, William J Kupsky, Lisa A Polin, Otto Muzik, Csaba Juhász, Sandeep Mittal
Increasing evidence demonstrates the immunosuppressive kynurenine pathway's (KP) role in the pathophysiology of human gliomas. To study the KP in vivo, we used the noninvasive molecular imaging tracer α-[(11)C]-methyl-l-tryptophan (AMT). The AMT-positron emission tomography (PET) has shown high uptake in high-grade gliomas and predicted survival in patients with recurrent glioblastoma (GBM). We generated patient-derived xenograft (PDX) models from dissociated cells, or tumor fragments, from 5 patients with GBM...
2016: Molecular Imaging
Paul J Akhenblit, Neale T Hanke, Alexander Gill, Daniel O Persky, Christine M Howison, Mark D Pagel, Amanda F Baker
AcidoCEST magnetic resonance imaging (MRI) has previously been shown to measure tumor extracellular pH (pHe) with excellent accuracy and precision. This study investigated the ability of acidoCEST MRI to monitor changes in tumor pHe in response to therapy. To perform this study, we used the Granta 519 human mantle cell lymphoma cell line, which is an aggressive B-cell malignancy that demonstrates activation of the phosphatidylinositol-3-kinase/Akt/mammalian target of rapamycin (mTOR) pathway. We performed in vitro and in vivo studies using the Granta 519 cell line to investigate the efficacy and associated changes induced by the mTOR inhibitor, everolimus (RAD001)...
2016: Molecular Imaging
Sofia M Pereira, Steve R Williams, Patricia Murray, Arthur Taylor
Bacterial genes involved in the biomineralization of magnetic nanoparticles in magnetotactic bacteria have recently been proposed as reporters for magnetic resonance imaging (MRI). In such systems, the expression of the bacterial genes in mammalian cells purportedly leads to greater concentrations of intracellular iron or the biomineralization of iron oxides, thus leading to an enhancement in relaxation rate that is detectable via MRI. Here, we show that the constitutive expression of the magA gene from Magnetospirillum magnetotacticum is tolerated by human embryonic kidney (HEK) cells but induces a strong toxic effect in murine mesenchymal/stromal cells and kidney-derived stem cells, severely restricting its effective use as a reporter gene for stem cells...
2016: Molecular Imaging
Qiao He, Xinchong Shi, Linqi Zhang, Chang Yi, Xuezhen Zhang, Xiangsong Zhang
PURPOSE: The aim of this study was to investigate the role of de novo glutamine (Gln) synthesis in the proliferation of C6 glioma cells and its detection with (13)N-ammonia. METHODS: Chronic Gln-deprived C6 glioma (0.06C6) cells were established. The proliferation rates of C6 and 0.06C6 cells were measured under the conditions of Gln deprivation along with or without the addition of ammonia or glutamine synthetase (GS) inhibitor. (13)N-ammonia uptake was assessed in C6 cells by gamma counting and in rats with C6 and 0...
2016: Molecular Imaging
Clément Thomas, Johnny Vercouillie, Aurélie Doméné, Clovis Tauber, Michael Kassiou, Denis Guilloteau, Christophe Destrieux, Sophie Sérrière, Sylvie Chalon
Subarachnoid hemorrhage (SAH) can lead to delayed cerebral ischemia, which increases the rate of morbidity and mortality. The detection of microglial activation may serve as a biomarker for the identification of patients at risk of this deleterious consequence. We assessed this hypothesis in a rat model of SAH in which the exploration of neuroinflammation related to microglial activation was correlated with the degree of bleeding. We used the rat filament model and evaluated (at 48 hours postsurgery) the intensity of neuroinflammation using positron emission tomography (PET) imaging with the 18-kDa translocator protein (TSPO) tracer [(18)F]DPA-714, quantitative autoradiography with [(3)H]PK-11195, and SAH grade by postmortem brain picture...
2016: Molecular Imaging
Steven Deleye, Ann-Marie Waldron, Jill C Richardson, Mark Schmidt, Xavier Langlois, Sigrid Stroobants, Steven Staelens
INTRODUCTION: In this study, the influence of physiological determinants on 18F-fluoro-d-glucose ((18)F-FDG) brain uptake was evaluated in a mouse model of Alzheimer disease. MATERIALS AND METHODS: TASTPM (Tg) and age-matched C57BL/6 J (WT) mice were fasted for 10 hours, while another group was fasted for 20 hours to evaluate the effect of fasting duration. The effect of repeatedly scanning was evaluated by scanning Tg and WT mice at days 1, 4, and 7. Brain (18)F-FDG uptake was evaluated in the thalamus being the most indicative region...
2016: Molecular Imaging
Rui Luo, Lei Niu, Fan Qiu, Wei Fang, Tong Fu, Ming Zhao, Ying-Jian Zhang, Zi-Chun Hua, Xiao-Feng Li, Feng Wang
Our goal was to validate the feasibility of(99m)Tc-duramycin as a potential apoptosis probe for monitoring tumor response to paclitaxel in breast cancer xenografts. The binding of(99m)Tc-duramycin to phosphatidylethanolamine was validated in vitro using paclitaxel-treated human breast carcinoma MDA-MB-231 cells. Female BALB/c mice (n = 5) bearing breast cancer xenografts were randomized into 2 groups and intraperitoneally injected with 40 mg/kg paclitaxel or phosphate-buffered saline.(99m)Tc-duramycin (37-55...
2016: Molecular Imaging
Winn Aung, Atsushi B Tsuji, Hitomi Sudo, Aya Sugyo, Takako Furukawa, Yoshinori Ukai, Yoshikazu Kurosawa, Tsuneo Saga
To explore suitable imaging probes for early and specific detection of pancreatic cancer, we demonstrated that α6β4integrin is a good target and employed single-photon emission computed tomography (SPECT) or near-infrared (NIR) imaging for immunotargeting. Expression levels of α6β4were examined by Western blotting and flow cytometry in certain human pancreatic cancer cell lines. The human cell line BxPC-3 was used for α6β4-positive and a mouse cell line, A4, was used for negative counterpart. We labeled antibody against α6β4with Indium-111 ((111)In) or indocyanine green (ICG)...
2016: Molecular Imaging
Daniel Spira, Rüdiger Bantleon, Hartwig Wolburg, Fritz Schick, Gerd Groezinger, Jakub Wiskirchen, Benjamin Wiesinger
OBJECTIVES: To use the superparamagnetic iron oxide (SPIO) contrast agent Resovist (±transfection agent) to label human melanoma cells and determine its effects on cellular viability, microstructure, iron quantity, and magnetic resonance imaging (MRI) detectability. MATERIALS AND METHODS: Human SK-Mel28 melanoma cells were incubated with Resovist (±liposomal transfection agent DOSPER). The cellular iron content was measured, and labeled cells were examined at 1...
2016: Molecular Imaging
Jeyan S Kumar, Lisa M Miller Jenkins, Michael M Gottesman, Matthew D Hall
Cyclodextrins are well-characterized, barrel-shaped molecules that can solubilize organic small molecules in aqueous solution via host-guest interactions. As such, cyclodextrins are used as excipients for experimental therapeutics in vivo. We observed unanticipated modifications to bioluminescence imaging (BLI) signal intensity when 2-hydroxy-propyl-β-cyclodextrin (HPCD) was coinjected as an excipient. We hypothesized that HPCD bindsd-luciferin and interferes with the BLI signal. Using luciferase-expressing cell lines, we showed that HPCD lowers the BLI signal in a concentration-dependent manner...
2016: Molecular Imaging
Lieven Declercq, Sofie Celen, Joan Lecina, Muneer Ahamed, Thomas Tousseyn, Diederik Moechars, Jesus Alcazar, Manuela Ariza, Katleen Fierens, Astrid Bottelbergs, Jonas Mariën, Rik Vandenberghe, Ignacio Jose Andres, Koen Van Laere, Alfons Verbruggen, Guy Bormans
Early clinical results of two tau tracers, [(18)F]T808 and [(18)F]T807, have recently been reported. In the present study, the biodistribution, radiometabolite quantification, and competition-binding studies were performed in order to acquire comparative preclinical data as well as to establish the value of T808 and T807 as benchmark compounds for assessment of binding affinities of eight new/other tau tracers. Biodistribution studies in mice showed high brain uptake and fast washout.In vivoradiometabolite analysis using high-performance liquid chromatography showed the presence of polar radiometabolites in plasma and brain...
2016: Molecular Imaging
Pei Yuin Keng, R Michael van Dam
AbstractThe emerging technology of digital microfluidics is opening up the possibility of performing radiochemistry at the microliter scale to produce tracers for positron emission tomography (PET) labeled with fluorine-18 or other isotopes. Working at this volume scale not only reduces reagent costs but also improves specific activity (SA) by reducing contamination by the stable isotope. This technology could provide a practical means to routinely prepare high-SA tracers for applications such as neuroimaging and could make it possible to routinely achieve high SA using synthesis strategies such as isotopic exchange...
December 5, 2015: Molecular Imaging
Jian-Guo Wu, Shao-Li Song, Xiang Zhou, Fan Wang, Yin-Yan Zhu, Lei Xie, Fan Zhang, Gang Huang
AbstractPrevious studies have reported that 99mTc-3PRGD2 is an excellent tumor imaging agent that showed a good correlation with integrin αvβ3, a main factor of tumor-induced angiogenesis. In this study, we investigated the biometabolic distribution characteristics of 99mTc-3PRGD2 with a continuous dynamic acquisition mode to explore the potential value of 99mTc-3PRGD2 in monitoring chemotherapeutic effects in VX2 tumor models. Eighteen rabbits with 27 implanted VX2 squamous cell tumors were randomly divided into a nontreated control group (NTG, n = 8; 12 tumors) and a treatment group (TG, n = 10; 15 tumors)...
December 5, 2015: Molecular Imaging
Casey Y Lee, R Terry Thompson, Frank S Prato, Donna E Goldhawk, Neil Gelman
Reporter gene-based labeling of cells with iron is an emerging method of providing magnetic resonance imaging contrast for long-term cell tracking and monitoring cellular activities. This report investigates 9.4 T nuclear magnetic resonance properties of mammalian cells overexpressing MagA, a putative iron transport protein from magnetotactic bacteria. MagA-expressing MDA-MB-435 cells were cultured in the presence and absence of iron supplementation and compared to the untransfected control. The relationship between the transverse relaxation rate (R2) and interecho time was investigated using the Carr-Purcell-Meiboom-Gill sequence...
2015: Molecular Imaging
Aparna Baranwal, M Reza Mirbolooki, Jogeshwar Mukherjee
Metabolic activity of brown adipose tissue (BAT) is activated by β3-adrenoceptor agonists and norepinephrine transporter (NET) blockers and is measurable using [(18)F]fluorodeoxyglucose ([(18)F]FDG) positron emission tomography/computed tomography (PET/CT) in rats. Using the streptozotocin (STZ)-treated rat model of type 1 diabetes mellitus (T1DM), we investigated BAT activity in this rat model under fasting and nonfasting conditions using [(18)F]FDG PET/CT. Drugs that enhance BAT activity may have a potential for therapeutic development in lowering blood sugar in insulin-resistant diabetes...
2015: Molecular Imaging
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