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Molecular Imaging

Lee Josephson, Nancy Stratman, YuTing Liu, Fang Qian, Steven H Liang, Neil Vasdev, Shil Patel
Development of an α-synuclein (α-Syn) positron emission tomography agent for the diagnosis and evaluation of Parkinson disease therapy is a key goal of neurodegenerative disease research. BF-227 has been described as an α-Syn binder and hence was employed as a lead to generate a library of α-Syn-binding compounds. [3 H]BF-227 bound to α-Syn and amyloid β peptide (Aβ) fibrils with affinities (KD ) of 46.0 nM and 15.7 nM, respectively. Affinities of BF-227-like compounds (expressed as Ki ) for α-Syn and Aβ fibrils were determined, along with 5 reference compounds (flutafuranol, flutemetamol, florbetapir, BF-227, and PiB)...
January 2018: Molecular Imaging
Sara Zullino, Monica Argenziano, Ilaria Stura, Caterina Guiot, Roberta Cavalli
Ultrasound Contrast Agents (UCAs) consisting of gas-filled-coated Microbubbles (MBs) with diameters between 1 and 10 µm have been used for a number of decades in diagnostic imaging. In recent years, submicron contrast agents have proven to be a viable alternative to MBs for ultrasound (US)-based applications for their capability to extravasate and accumulate in the tumor tissue via the enhanced permeability and retention effect. After a short overview of the more recent approaches to ultrasound-mediated imaging and therapeutics at the nanoscale, phase-change contrast agents (PCCAs), which can be phase-transitioned into highly echogenic MBs by means of US, are here presented...
January 2018: Molecular Imaging
Lauren Kosten, Jeroen Verhaeghe, Leonie Wyffels, Sigrid Stroobants, Steven Staelens
Detecting changes in metabotropic glutamate receptor 5 (mGluR5) availability through molecular imaging with the positron emission tomography (PET) tracer [11 C]ABP688 is valuable for studying dysfunctional glutamate transmission associated with neuropsychiatric disorders. Using an infusion protocol in rats, we visualized the acute effect of subanesthetic doses of ketamine on mGluR5 in rat brain. Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist known to increase glutamate release. Imaging was performed with a high-affinity PET ligand [11 C]ABP688, a negative allosteric modulator of mGluR5...
January 2018: Molecular Imaging
Vidya Narayanaswami, Kenneth Dahl, Vadim Bernard-Gauthier, Lee Josephson, Paul Cumming, Neil Vasdev
The dynamic and multicellular processes of neuroinflammation are mediated by the nonneuronal cells of the central nervous system, which include astrocytes and the brain's resident macrophages, microglia. Although initiation of an inflammatory response may be beneficial in response to injury of the nervous system, chronic or maladaptive neuroinflammation can have harmful outcomes in many neurological diseases. An acute neuroinflammatory response is protective when activated neuroglia facilitate tissue repair by releasing anti-inflammatory cytokines and neurotrophic factors...
January 2018: Molecular Imaging
Mariya Shapovalova, Sean R Pyper, Branden S Moriarity, Aaron M LeBeau
The recent success of autologous T cell-based therapies in hematological malignancies has spurred interest in applying similar immunotherapy strategies to the treatment of solid tumors. Identified nearly 4 decades ago, natural killer (NK) cells represent an arguably better cell type for immunotherapy development. Natural killer cells are cytotoxic lymphocytes that mediate the direct killing of transformed cells with reduced or absent major histocompatibility complex (MHC) and are the effector cells in antibody-dependent cell-mediated cytotoxicity...
January 2018: Molecular Imaging
Jade E Jones, Susheel Bhanu Busi, Jonathan B Mitchem, James M Amos-Landgraf, Michael R Lewis
The goal of these studies was to use a tumor-targeting, near-infrared (NIR) fluorescent peptide to evaluate early detection and to guide surgical removal of polyps in a genetically engineered rat model of spontaneous colorectal cancer. This peptide, LS301, was conjugated to Cy7.5 and applied topically to the colon of adenoma-bearing Pirc rats. Ten minutes after administration, rats underwent targeted NIR laser colonoscopy. Rats were also evaluated by white light colonoscopy and narrow-band imaging, for comparison to the NIR technique...
January 2018: Molecular Imaging
Mehdi Shirin Shandiz, Hamid Saligheh Rad, Pardis Ghafarian, Khadijeh Yaghoubi, Mohammad Reza Ay
PURPOSE: Prostate imaging is a major application of hybrid positron emission tomography/magnetic resonance imaging (PET/MRI). Currently, MRI-based attenuation correction (MRAC) for whole-body PET/MRI in which the bony structures are ignored is the main obstacle to successful implementation of the hybrid modality in the clinical work flow. Ultrashort echo time sequence captures bone signal but needs specific hardware-software and is challenging in large field of view (FOV) regions, such as pelvis...
January 2018: Molecular Imaging
Frezghi Habte, Arutselvan Natarajan, David S Paik, Sanjiv Sam Gambhir
Cerenkov luminescence imaging (CLI) is commonly performed using two-dimensional (2-D) conventional optical imaging systems for its cost-effective solution. However, quantification of CLI comparable to conventional three-dimensional positron emission tomography (PET) is challenging using these systems due to both the high attenuation of Cerenkov radiation (CR) on mouse tissue and nonexisting depth resolution of CLI using 2-D imaging systems (2-D CLI). In this study, we developed a model that estimates effective tissue attenuation coefficient and corrects the tissue attenuation of CLI signal intensity independent of tissue depth and size...
January 2018: Molecular Imaging
Joseph E Kobes, George I Georgiev, Anthony V Louis, Isen A Calderon, Eriko S Yoshimaru, Louie M Klemm, Douglas W Cromey, Zain Khalpey, Mark D Pagel
Reseeding of decellularized organ scaffolds with a patient's own cells has promise for eliminating graft versus host disease. This study investigated whether ultrasound imaging or magnetic resonance imaging (MRI) can track the reseeding of murine liver scaffolds with silica-labeled or iron-labeled liver hepatocytes. Mesoporous silica particles were created using the Stöber method, loaded with Alexa Flour 647 fluorophore, and conjugated with protamine sulfate, glutamine, and glycine. Fluorescent iron oxide particles were obtained from a commercial source...
January 2018: Molecular Imaging
Pedro Brugarolas, Daniel S Reich, Brian Popko
Noninvasive imaging of demyelination and remyelination is critical for diagnosis and clinical management of demyelinating diseases. Positron emission tomography (PET) has the potential to complement magnetic resonance imaging (MRI) by providing a quantitative measure specific to demyelination. In Brugarolas et al's study 1 , we describe the development of the first PET tracer for voltage-gated K+ channels based on a clinically approved drug for multiple sclerosis that can be used for imaging demyelination in animal models...
January 2018: Molecular Imaging
Masaru Ishihara, Masahisa Onoguchi, Takayuki Shibutani
The aim of this study was to assess the washout rate (WOR) for thallium-201-chloride single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) using cadmium zinc telluride detectors for SPECT (CZT SPECT) versus conventional Anger-type SPECT (conventional SPECT). A total of 52 Japanese patients were examined using CZT SPECT and conventional SPECT, and the global WORs were compared. Additionally, the MPI WORs were compared for patients with a normal MPI versus those in whom MPI reflected the patients' multivessel disease (MVD) MPI...
January 2018: Molecular Imaging
Kambiz Rahbar, Ali Afshar-Oromieh, Hossein Jadvar, Hojjat Ahmadzadehfar
Prostate-specific membrane antigen (PSMA) is a promising target for imaging diagnostics and targeted radionuclide therapy (theranostics) of prostate cancer and its metastases. There is increasing evidence of encouraging response rates and a low toxicity profile of radioligand therapy (RLT) of metastatic castration-resistant prostate cancer using 177 Lu-labeled PSMA ligands. In this article, we review the current status of diagnostics and therapy using radiolabeled PSMA ligands. We also suggest protocols for patient selection criteria and conduct of PSMA-based RLT...
January 2018: Molecular Imaging
Yongfeng Zhao, Bo Pang, Lisa Detering, Hannah Luehmann, Miaoxin Yang, Kvar Black, Deborah Sultan, Younan Xia, Yongjian Liu
PURPOSE: Melanoma is a lethal skin cancer with unmet clinical needs for targeted imaging and therapy. Nanoscale materials conjugated with targeting components have shown great potential to improve tumor delivery efficiency while minimizing undesirable side effects in vivo. Herein, we proposed to develop targeted nanoparticles for melanoma theranostics. METHOD: In this work, gold nanocages (AuNCs) were conjugated with α-melanocyte-stimulating hormone (α-MSH) peptide and radiolabeled with 64 Cu for melanocortin 1 receptor-(MC1R) targeted positron emission tomography (PET) in a mouse B16/F10 melanoma model...
January 2018: Molecular Imaging
Govindarajan Srimathveeravalli, Dalya Abdel-Atti, Carlos Pérez-Medina, Haruyuki Takaki, Stephen B Solomon, Willem J M Mulder, Thomas Reiner
Reversible electroporation (RE) can facilitate nanoparticle delivery to tumors through direct transfection and from changes in vascular permeability. We investigated a radiolabeled liposomal nanoparticle (89 Zr-NRep) for monitoring RE-mediated liposomal doxorubicin (DOX) delivery in mouse tumors. Intravenously delivered 89 Zr-NRep allowed positron emission tomography imaging of electroporation-mediated nanoparticle uptake. The relative order of 89 Zr-NRep injection and electroporation did not result in significantly different overall tumor uptake, suggesting direct transfection and vascular permeability can independently mediate deposition of 89 Zr-NRep in tumors...
January 2018: Molecular Imaging
Adriana V F Massicano, Bernadette V Marquez-Nostra, Suzanne E Lapi
Since its discovery, the human epidermal growth factor 2 (HER2) has been extensively studied. Presently, there are 2 standard diagnostic techniques to assess HER2 status in biopsies: immunohistochemistry and fluorescence in situ hybridization. While these techniques have played an important role in the treatment of patients with HER2-positive cancer, they both require invasive biopsies for analysis. Moreover, the expression of HER2 is heterogeneous in breast cancer and can change over the course of the disease...
January 2018: Molecular Imaging
Andrew W Stephens, Norman Koglin, Ludger M Dinkelborg
Thrombus formation can lead to heart attacks, stroke and pulmonary embolism, which are major causes of mortality. Current standard diagnostic imaging methods detect anatomic abnormalities such as vascular flow impairment but have limitations. By using a targeted molecular imaging approach critical components of a pathology can be selectively visualized and exploited for an improved diagnosis and patient management. The GPIIb/IIIa receptor is abundantly and specifically exposed on activated platelets and is the key receptor in thrombus formation...
January 2018: Molecular Imaging
Su Xu, Wenjun Zhu, Yamin Wan, JiaBei Wang, Xi Chen, Liya Pi, Mary Kay Lobo, Bin Ren, Zhekang Ying, Michael Morris, Qi Cao
Minimal hepatic encephalopathy (MHE) is highly prevalent, observed in up to 80% of patients with liver dysfunction. Minimal hepatic encephalopathy is defined as hepatic encephalopathy with cognitive deficits and no grossly evident neurologic abnormalities. Clinical management may be delayed due to the lack of in vivo quantitative methods needed to reveal changes in brain neurobiochemical biomarkers. To gain insight into the development of alcoholic liver disease-induced neurological dysfunction (NDF), a mouse model of late-stage alcoholic liver fibrosis (LALF) was used to investigate changes in neurochemical levels in the thalamus and hippocampus that relate to behavioral changes...
January 2018: Molecular Imaging
Stephen M Chrzanowski, Ravneet S Vohra, Brittany A Lee-McMullen, Abhinandan Batra, Ray A Spradlin, Jazmine Morales, Sean Forbes, Krista Vandenborne, Elisabeth R Barton, Glenn A Walter
Assessment of muscle pathology is a key outcome measure to measure the success of clinical trials studying muscular dystrophies; however, few robust minimally invasive measures exist. Indocyanine green (ICG)-enhanced near-infrared (NIR) optical imaging offers an objective, minimally invasive, and longitudinal modality that can quantify pathology within muscle by imaging uptake of ICG into the damaged muscles. Dystrophic mice lacking dystrophin (mdx) or gamma-sarcoglycan (Sgcg-/- ) were compared to control mice by NIR optical imaging and magnetic resonance imaging (MRI)...
January 2017: Molecular Imaging
Bok-Nam Park, Su Jin Lee, Jung Hyun Roh, Kyung-Han Lee, Young-Sil An, Joon-Kee Yoon
INTRODUCTION: The potential of a radioiodine-labeled, anti-adenosine triphosphate synthase monoclonal antibody (ATPS mAb) as a theragnostic agent for simultaneous cancer imaging and treatment was evaluated. METHODS: Adenosine triphosphate synthase monoclonal antibody was labeled with radioiodine, then radiotracer uptake was measured in 6 different cancer cell lines. In vivo biodistribution was evaluated 24 and 48 hours after intravenous injection of125 I-ATPS mAb into MKN-45 tumor-bearing mice (n = 3)...
January 2017: Molecular Imaging
Chengcheng Zhang, Kuo-Shyan Lin, François Bénard
Melanoma is a deadly disease at late metastatic stage, and early diagnosis and accurate staging remain the key aspects for managing melanoma. The melanocortin 1 receptor (MC1 R) is overexpressed in primary and metastatic melanomas, and its endogenous ligand, the α-melanocyte-stimulating hormone (αMSH), has been extensively studied for the development of MC1 R-targeted molecular imaging and therapy of melanoma. Natural αMSH is not well suited for this purpose due to low stability in vivo. Unnatural amino acid substitutions substantially stabilized the peptide, while cyclization via lactam bridge and metal coordination further improved binding affinity and stability...
January 2017: Molecular Imaging
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