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https://www.readbyqxmd.com/read/28409338/fluorine-18-labeling-of-the-her2-targeting-single-domain-antibody-2rs15d-using-a-residualizing-label-and-preclinical-evaluation
#1
Zhengyuan Zhou, Ganesan Vaidyanathan, Darryl McDougald, Choong Mo Kang, Irina Balyasnikova, Nick Devoogdt, Angeline N Ta, Brian R McNaughton, Michael R Zalutsky
PURPOSE: Our previous studies with F-18-labeled anti-HER2 single-domain antibodies (sdAbs) utilized 5F7, which binds to the same epitope on HER2 as trastuzumab, complicating its use for positron emission tomography (PET) imaging of patients undergoing trastuzumab therapy. On the other hand, sdAb 2Rs15d binds to a different epitope on HER2 and thus might be a preferable vector for imaging in these patients. The aim of this study was to evaluate the tumor targeting of F-18 -labeled 2Rs15d in HER2-expressing breast carcinoma cells and xenografts...
April 13, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28398234/down-regulated-drebrin-aggravates-cognitive-impairments-in-a-mouse-model-of-alzheimer-s-disease
#2
Yan Liu, Yanfeng Xu, Ling Zhang, Lan Huang, Pin Yu, Hua Zhu, Wei Deng, Chuan Qin
The developmentally regulated brain protein drebrin (Dbn) is a functional protein involved with long-term memory formation and is widely distributed in brain neurons, especially in the dendritic spines. A noticeable decline of this protein has been found in the hippocampus and cortex of patients with Alzheimer's disease (AD), yet the relationship between Dbn and AD has not been fully understood. In the present study, we examined how down-regulation of Dbn impacts the progression of AD in experimental animals...
April 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28393895/sex-differences-in-regional-brain-glucose-metabolism-following-opioid-withdrawal-and-replacement
#3
Giovanni C Santoro, Joseph Carrion, Krishna Patel, Crystal Vilchez, Jennifer Veith, Jonathan D Brodie, Stephen L Dewey
Methadone and buprenorphine are currently the most common pharmacological treatments for opioid dependence. Interestingly, the clinical response to these drugs appears to be sex-specific. That is, females exhibit superior therapeutic efficacy, defined as extended periods of abstinence and longer time to relapse, compared to males. However, the underlying metabolic effects of opioid withdrawal and replacement have not been examined. Therefore, using (18)FDG and microPET, we measured differences in regional brain glucose metabolism in males and females following morphine withdrawal and subsequent methadone or buprenorphine replacement...
April 10, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28365375/preclinical-molecular-imaging-of-glutamatergic-and-dopaminergic-neuroreceptor-kinetics-in-obsessive-compulsive-disorder
#4
S Servaes, D Glorie, J Verhaeghe, S Stroobants, S Staelens
BACKGROUND: Molecular neuroimaging was applied in the quinpirole rat model for compulsive checking in OCD to visualize the D2- and mGluR5-receptor occupancy with Raclopride and ABP-688 microPET/CT. METHODS: Animals (n=48) were exposed to either saline (CTRL; 1mL/kg) or quinpirole (QP; dopamine D2-agonist, 0.5mg/kg) in a single injection (RAC and ABP acute groups) or twice-weekly during 7weeks (chronic group). Animals underwent PET/CT after the 1st injection (acute) or before initial exposure and following the 10th injection in week 5 (chronic)...
March 30, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28360206/her3-specific-biodistribution-and-tumor-uptake-of-89-zr-msb0010853-visualized-by-real-time-and-non-invasive-pet-imaging
#5
Frank-Jan Warnders, Anton Gt Terwisscha van Scheltinga, Christine Knuehl, Maarten van Roy, Erik F de Vries, Jos G W Kosterink, Elisabeth G E de Vries, Marjolijn N Lub-de Hooge
The human epidermal growth factor receptor (HER)3 is an interesting target for antitumor therapy. For optimal HER3 signaling inhibition a biparatopic Nanobody® construct (MSB0010853) was developed which binds two HER3 epitopes. In addition, MSB0010853 contains a third Nanobody that binds albumin to extend its circulation time. MSB0010853 is cross-reactive with HER3 and albumin of mouse origin. We aimed to gain insight in MSB0010853 biodistribution and tumor uptake by radiolabeling the Nanobody construct with (89)Zr...
March 30, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28347826/changes-in-cerebral-18-f-fdg-uptake-induced-by-acute-alcohol-administration-in-a-rat-model-of-alcoholism
#6
Juan D Gispert, Francisca P Figueiras, Valentina Vengeliene, José R Herance, Santiago Rojas, Rainer Spanagel
Several [(18)F]-FDG positron emission tomography (PET) studies in alcoholics have consistently reported decreases in overall brain glucose metabolism at rest and following acute alcohol administration. However, changes in cerebral glucose utilization associated with the transition to addiction are not well understood and require longitudinal translational imaging studies in animal models of alcoholism. Here, we studied brain glucose uptake in alcohol drinking rats in order to provide convergent evidence to what has previously been reported in human studies...
March 27, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28302035/translational-multimodality-neuroimaging
#7
Sushil K Sharma
Recently high-resolution, noninvasive, multimodality in-vivo molecular imaging with PET, SPECT, CT and MRI, employing fusion algorithms has revolutionized personalized medicine. However, specific radiopharmaceuticals (RPs) for the accurate diagnosis and effective treatment of progressive neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, drug addiction, and other cognitive impairments still remain in developmental phase. Currently, multimodality fusion neuroimaging is utilized for the determination of: pharmacokinetics and pre-clinical development of radiopharmaceuticals (RPs); in-vivo monitoring of stem cell transplantation therapy; nicotinic acetylcholine receptors (nAChRs) investigations; and regional cerebral blood flow and glucose metabolism in cognitively-impaired subjects employing noninvasive microPET and nano-SPECT imaging...
March 15, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28255357/stat3-nf-%C3%AE%C2%BAb-regulated-lentiviral-tk-gcv-suicide-gene-therapy-for-cisplatin-resistant-triple-negative-breast-cancer
#8
Wei-Ying Kuo, Luen Hwu, Chun-Yi Wu, Jhih-Shian Lee, Chi-Wei Chang, Ren-Shyan Liu
Triple-negative breast cancer (TNBC) represents approximately 20% of all breast cancers and appears resistance to conventional cytotoxic chemotherapy, demonstrating a particularly poor prognosis and a significantly worse clinical outcome than other types of cancer. Suicide gene therapy has been used for the in vivo treatment of various solid tumors in recent clinical trials. In tumor microenvironment, STAT3/NF-κB pathways are constitutively activated in stromal cells as well as in cancer stem cells (CSCs)...
2017: Theranostics
https://www.readbyqxmd.com/read/28243322/targeting-metabolic-remodeling-in-triple-negative-breast-cancer-in-a-murine-model
#9
Verónica García-Castillo, Eduardo López-Urrutia, Octavio Villanueva-Sánchez, Miguel Á Ávila-Rodríguez, Alejandro Zentella-Dehesa, Carlo Cortés-González, César López-Camarillo, Nadia J Jacobo-Herrera, Carlos Pérez-Plasencia
Background: Chemotherapy is the backbone of systemic treatment for triple negative breast cancer (TNBC), which is one of the most relevant breast cancers molecular types due to the ability of tumor cells to develop drug resistance, highlighting the urgent need to design newer and safer drug combinations for treatment. In this context, to overcome tumor cell drug resistance, we employed a novel combinatorial treatment including Doxorubicin, Metformin, and Sodium Oxamate (DoxMetOx). Such pharmacological combination targets indispensable hallmarks of cancer-related to aerobic glycolysis and DNA synthesis...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28239334/micropet-outperforms-beta-microprobes-in-determining-neuroreceptor-availability-under-pharmacological-restriction-for-cold-mass-occupancy
#10
Dorien Glorie, Stijn Servaes, Jeroen Verhaeghe, Tine Wyckhuys, Leonie Wyffels, Olivier Vanderveken, Sigrid Stroobants, Steven Staelens
Both non-invasive micro-positron emission tomography (μPET) and in situ beta-microprobes have the ability to determine radiotracer kinetics and neuroreceptor availability in vivo. Beta-microprobes were proposed as a cost-effective alternative to μPET, but literature revealed conflicting results most likely due to methodological differences and inflicted tissue damage. The current study has three main objectives: (i) evaluate the theoretical advantages of beta-microprobes; (ii) perform μPET imaging to assess the impact of (beta-micro)probe implantation on relative tracer delivery (R1) and receptor occupancy (non-displaceable binding potential, BPND) in the rat brain; and (iii) investigate whether beta-microprobe recordings produce robust results when a pharmacological restriction for cold mass dose (tracer dose condition) is imposed...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28184015/dual-pi3k-mtor-inhibition-in-colorectal-cancers-with-apc-and-pik3ca-mutations
#11
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)...
February 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
#12
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...
February 2017: Anticancer Research
https://www.readbyqxmd.com/read/28159919/evaluation-of-radiofluorinated-carboximidamides-as-potential-ido-targeted-pet-tracers-for-cancer-imaging
#13
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
#14
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
#15
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
#16
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
#17
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...
February 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28078167/a-novel-strategy-for-attenuating-opioid-withdrawal-in-neonates
#18
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
#19
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
#20
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
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