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"small animal PET"

Kazunori Kawamura, Yoko Shimoda, Joji Yui, Yiding Zhang, Tomoteru Yamasaki, Hidekatsu Wakizaka, Akiko Hatori, Lin Xie, Katsushi Kumata, Masayuki Fujinaga, Masanao Ogawa, Yusuke Kurihara, Nobuki Nengaki, Ming-Rong Zhang
INTRODUCTION: A positron emission tomography (PET) probe with ultra-high specific radioactivity (SA) enables measuring high receptor specific binding in brain regions by avoiding mass effect of the PET probe itself. It has been reported that PET probe with ultra-high SA can detect small change caused by endogenous or exogenous ligand. Recently, Kealey et al. developed [(11)C]BU99008, a more potent PET probe for I2-imidazoline receptors (I2Rs) imaging, with a conventional SA (mean 76GBq/μmol) showed higher specific binding in the brain...
October 26, 2016: Nuclear Medicine and Biology
Yangchun Xin, Hancheng Cai
PURPOSE: Tryptophan metabolism via indoleamine 2,3-dioxygenase (IDO)-mediated kynurenine pathway plays a role in immunomodulation and has been emerging as a plausible target for cancer immunotherapy. Imaging IDO-mediated kynurenine pathway of tryptophan metabolism with positron emission tomography (PET) could provide valuable information for noninvasive assessment of cancer immunotherapy response. In this work, radiotracer 1-(2-[(18)F]fluoroethyl)-L-tryptophan (1-L-[(18)F]FETrp) and its enantioisomer 1-D-[(18)F]FETrp were synthesized and evaluated for PET imaging of IDO-mediated kynurenine pathway of tryptophan metabolism...
November 4, 2016: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
Chi-Cheng Huang, Chun-Hu Wu, Ya-Yao Huang, Kai-Yuan Tzen, Szu-Fu Chen, Miao-Ling Tsai, Hsiao-MIng Wu
: Performing quantitative small animal positron emission tomography (qµPET) with arterial input function was considered technically challenging. Here, we introduce a catheterization procedure which keeps a rat physiologically stable for 1.5 months. We demonstrated the feasibility of qµPET by performing repeated (18)F-FDG qµPET to monitor the time-course of cerebral metabolic rates of glucose (cMRglc) variations in rats. METHODS: Aseptic surgeries were performed on two rats...
October 27, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
J D Thiessen, E Shams, G Stortz, G Schellenberg, D Bishop, M S Khan, P Kozlowski, F Retière, V Sossi, C J Thompson, A L Goertzen
A full-ring PET insert consisting of 16 PET detector modules was designed and constructed to fit within the 114 mm diameter gradient bore of a Bruker 7 T MRI. The individual detector modules contain two silicon photomultiplier (SiPM) arrays, dual-layer offset LYSO crystal arrays, and high-definition multimedia interface (HDMI) cables for both signal and power transmission. Several different RF shielding configurations were assessed prior to construction of a fully assembled PET insert using a combination of carbon fibre and copper foil for RF shielding...
November 21, 2016: Physics in Medicine and Biology
Mathias Kranz, Bernhard Sattler, Solveig Tiepolt, Stephan Wilke, Winnie Deuther-Conrad, Cornelius K Donat, Steffen Fischer, Marianne Patt, Andreas Schildan, Jörg Patt, René Smits, Alexander Hoepping, Jörg Steinbach, Osama Sabri, Peter Brust
BACKGROUND: Both enantiomers of [(18)F]flubatine are new radioligands for neuroimaging of α4β2 nicotinic acetylcholine receptors with positron emission tomography (PET) exhibiting promising pharmacokinetics which makes them attractive for different clinical questions. In a previous preclinical study, the main advantage of (+)-[(18)F]flubatine compared to (-)-[(18)F]flubatine was its higher binding affinity suggesting that (+)-[(18)F]flubatine might be able to detect also slight reductions of α4β2 nAChRs and could be more sensitive than (-)-[(18)F]flubatine in early stages of Alzheimer's disease...
December 2016: EJNMMI Physics
Paul R Territo, Amanda A Riley, Brian P McCarthy, Gary D Hutchins
Recent advancements in PET instrumentation have made the non-invasive assessment of cardiovascular function in small animals a reality. The majority of small animal PET systems use stationary detector gantries, thus affording high temporal resolution imaging of cardiac function. Systems designed to maximize spatial resolution and detection sensitivity employing rotating gantry designs are suboptimal when high temporal resolution imaging is needed. To overcome this limitation, the current work developed a novel view-sharing data analysis scheme suitable for dynamic cardiac PET imaging using (18)F-NaF as the tracer and tracer kinetic model analysis...
December 2016: EJNMMI Physics
Simone Maschauer, Marcus Heilmann, Carmen Wängler, Ralf Schirrmacher, Olaf Prante
Short synthetic octapeptide analogs derived from the native somatostatin peptides SST-14 and SST-28, namely octreotate (TATE) or octreotide (TOC), bind with high affinity to somatostatin receptors (sstr), mainly to subtypes 2 and 5, which are expressed in high density on neuroendocrine tumors (NET). Therefore, radiolabeled TATE or TOC derivatives represent highly valuable imaging probes for NET diagnosis by positron emission tomography (PET). The aim of our study was the development of an 18F-labeled octreotate analog as an alternative radiotracer for the clinically established 68Ga-DOTATOC and 68Ga-DOTATATE...
October 7, 2016: Bioconjugate Chemistry
Anna Schweifer, Florian Maier, Walter Ehrlichmann, Denis Lamparter, Manfred Kneilling, Bernd J Pichler, Friedrich Hammerschmidt, Gerald Reischl
INTRODUCTION: Radiolabeled 2-nitroimidazoles (azomycins) are a prominent class of biomarkers for PET imaging of hypoxia. [(18)F]Fluoro-azomycin-α-arabinoside ([(18)F]FAZA) - already in clinical use - may be seen as α-configuration nucleoside, but enters cells only via diffusion and is not transported by cellular nucleoside transporters. To enhance image contrast in comparison to [(18)F]FAZA our objective was to (18)F-radiolabel an azomycin-2´-deoxyriboside with β-configuration ([(18)F]FAZDR, [(18)F]-β-8) to mimic nucleosides more closely and comparatively evaluate it versus [(18)F]FAZA...
December 2016: Nuclear Medicine and Biology
Isabel Hinsenkamp, Sandra Schulz, Mareike Roscher, Anne-Maria Suhr, Björn Meyer, Bogdan Munteanu, Jens Fuchser, Stefan O Schoenberg, Matthias P A Ebert, Björn Wängler, Carsten Hopf, Elke Burgermeister
Gastric cancer (GC) remains a malignant disease with high mortality. Patients are frequently diagnosed in advanced stages where survival prognosis is poor. Thus, there is high medical need to find novel drug targets and treatment strategies. Recently, the comprehensive molecular characterization of GC subtypes revealed mutations in the small GTPase RHOA as a hallmark of diffuse-type GC. RHOA activates RHO-associated protein kinases (ROCK1/2) which regulate cell contractility, migration and growth and thus may play a role in cancer...
August 2016: Neoplasia: An International Journal for Oncology Research
Marian Meckel, Vojtěch Kubíček, Petr Hermann, Matthias Miederer, Frank Rösch
Radiolabeled bisphosphonates are commonly used in the diagnosis and therapy of bone metastases. Blood clearance of bisphosphonates is usually fast and only 30%-50% of the injected activity is retained in the skeleton, while most of the activity is excreted by the urinary tract. A longer blood circulation may enhance accumulation of bisphosphonate compounds in bone metastases. Therefore, a chemically modified macrocyclic bisphosphonate derivative with an additional human albumin binding entity was synthesized and pharmacokinetics of its complex was evaluated...
August 1, 2016: Nuclear Medicine and Biology
H Alva-Sánchez, C Quintana-Bautista, A Martínez-Dávalos, M A Ávila-Rodríguez, M Rodríguez-Villafuerte
In this work an experimental investigation was carried out to study the effect that positron range has over positron emission tomography (PET) scans through measurements of the line spread function (LSF) in tissue-equivalent materials. Line-sources consisted of thin capillary tubes filled with (18)F, (13)N or (68)Ga water-solution inserted along the axis of symmetry of cylindrical phantoms constructed with the tissue-equivalent materials: lung (inhale and exhale), adipose tissue, solid water, trabecular and cortical bone...
September 7, 2016: Physics in Medicine and Biology
Franziska Eckert, Julia Schmitt, Daniel Zips, Marcel A Krueger, Bernd J Pichler, Stephen D Gillies, Wolfgang Strittmatter, Rupert Handgretinger, Karin Schilbach
PURPOSE: NHS-IL12 is an immunocytokine targeting necrotic tumour areas. IL12 shows anti-tumour activity. As local irradiation might induce additional necrosis in solid tumours, we aimed to evaluate the increase in intratumoural accumulation of NHS-IL12 after irradiation and correlate the findings with diffusion-weighted MRI studies in two xenograft models. METHODS: Human rhabdomyosarcoma (A204) and prostate cancer (PC3) cells were studied in vitro and as subcutaneous xenografts...
August 2016: Cancer Immunology, Immunotherapy: CII
Simone Maschauer, Jürgen Einsiedel, Harald Hübner, Peter Gmeiner, Olaf Prante
The neurotensin (NT) receptor-1 (NTS1) is overexpressed in a variety of carcinomas and is therefore an interesting target for imaging with positron emission tomography (PET). The aim of this study was the development of new NT derivatives based on the metabolically stable peptide sequence NLys-Lys-Pro-Tyr-Tle-Leu suitable for PET imaging. The NT peptides were synthesized by solid-phase supported peptide synthesis and elongated with respective chelators (NODA-GA, DOTA) for (68)Ga-labeling or propargylglycine for (18)F-labeling via copper-catalyzed azide-alkyne cycloaddition...
July 14, 2016: Journal of Medicinal Chemistry
Amit Kumar, Tara Mastren, Bin Wang, Jer-Tsong Hsieh, Guiyang Hao, Xiankai Sun
Targeted therapy has become an effective strategy of precision medicine for cancer treatment. Based on the success of antibody-drug conjugates (ADCs), here we report a theranostic design of small-molecule drug conjugates (T-SMDCs) for targeted imaging and chemotherapy of prostate cancer. The structure of T-SMDCs built upon a polyethylene glycol (PEG) scaffold consists of (i) a chelating moiety for positron emission tomography (PET) imaging when labeled with (68)Ga, a positron-emitting radioisotope; (ii) a prostate specific membrane antigen (PSMA) specific ligand for prostate cancer targeting; and (iii) a cytotoxic drug (DM1) for chemotherapy...
July 20, 2016: Bioconjugate Chemistry
Mohammed K Hankir, Mathias Kranz, Thorsten Gnad, Juliane Weiner, Sally Wagner, Winnie Deuther-Conrad, Felix Bronisch, Karen Steinhoff, Julia Luthardt, Nora Klöting, Swen Hesse, John P Seibyl, Osama Sabri, John T Heiker, Matthias Blüher, Alexander Pfeifer, Peter Brust, Wiebke K Fenske
Phosphodiesterase type 10A (PDE10A) is highly enriched in striatum and is under evaluation as a drug target for several psychiatric/neurodegenerative diseases. Preclinical studies implicate PDE10A in the regulation of energy homeostasis, but the mechanisms remain unclear. By utilizing small-animal PET/MRI and the novel radioligand [(18)F]-AQ28A, we found marked levels of PDE10A in interscapular brown adipose tissue (BAT) of mice. Pharmacological inactivation of PDE10A with the highly selective inhibitor MP-10 recruited BAT and potentiated thermogenesis in vivo In diet-induced obese mice, chronic administration of MP-10 caused weight loss associated with increased energy expenditure, browning of white adipose tissue, and improved insulin sensitivity...
2016: EMBO Molecular Medicine
Nimali P Withana, Toshinobu Saito, Xiaowei Ma, Megan Garland, Changhao Liu, Hisanori Kosuge, Myriam Amsallem, Martijn Verdoes, Leslie O Ofori, Michael Fischbein, Mamoru Arakawa, Zhen Cheng, Michael V McConnell, Matthew Bogyo
: Macrophages are cellular mediators of vascular inflammation and are involved in the formation of atherosclerotic plaques. These immune cells secrete proteases such as matrix metalloproteinases and cathepsins that contribute to disease formation and progression. Here, we demonstrate that activity-based probes (ABPs) targeting cysteine cathepsins can be used in murine models of atherosclerosis to non-invasively image activated macrophage populations using both optical and PET/CT methods...
May 19, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Junwei Du, Yongfeng Yang, Xiaowei Bai, Martin S Judenhofer, Eric Berg, Kun Di, Steve Buckley, Carl Jackson, Simon R Cherry
The performance of an 8 × 8 array of 6.0 × 6.0 mm(2) (active area) SiPMs was evaluated for PET applications using crystal arrays with different pitch sizes (3.4 mm, 1.5 mm, 1.35 mm and 1.2 mm) and custom designed five-channel front-end readout electronics (four channels for position information and one channel for timing information). The total area of this SiPM array is 57.4 × 57.4 mm(2), and the pitch size is 7.2 mm. It was fabricated using enhanced blue sensitivity SiPMs (MicroFB-60035-SMT) with peak spectral sensitivity at 420 nm...
February 2016: IEEE Transactions on Nuclear Science
Valery Radchenko, Penelope Bouziotis, Theodoros Tsotakos, Mari Paravatou-Petsotas, Ana de la Fuente, George Loudos, Adrian L Harris, Stavros Xanthopoulos, Dmitry Filosofov, Harald Hauser, Michael Eisenhut, Bernard Ponsard, Frank Roesch
The application of radionuclide-labeled biomolecules such as monoclonal antibodies or antibody fragments for imaging purposes is called immunoscintigraphy. More specifically, when the nuclides used are positron emitters, such as zirconium-89, the technique is referred to as immuno-PET. Currently, there is an urgent need for radionuclides with a half-life which correlates well with the biological kinetics of the biomolecules under question and which can be attached to the proteins by robust labeling chemistry...
May 2016: Nuclear Medicine and Biology
Huahui Zeng, Xiangxiang Wu, Fahuan Song, Caiyun Xu, Hao Liu, Wendi Liu
We developed a radiosynthesis of the voltage sensitive tracer [(18)F]-fluoromethyltriphenylphosphonium cation ([(18)F]-FTPMP), giving high yield (30-34%, decay-corrected), radiochemical purity (>99%) and specific activity (about 760 GBq/μmol). [(18)F]-FTPMP had suitable lipophilicity (logP = 0.91 ± 0.03) and high in vivo/vitro stability. Biodistribution studies showed that [(18)F]-FTPMP had high heart uptake (>7%ID/g from 10 min to 120 min postinjection) and rapid clearance from the background...
August 8, 2016: European Journal of Medicinal Chemistry
Jürgen W A Sijbesma, Xiaoyun Zhou, David Vállez García, Martin C Houwertjes, Janine Doorduin, Chantal Kwizera, Bram Maas, Peter Meerlo, Rudi A Dierckx, Riemer H J A Slart, Philip H Elsinga, Aren van Waarde
PURPOSE: Small animal positron emission tomography (PET) can be used to detect small changes in neuroreceptor availability. This often requires rapid arterial blood sampling. However, current catheterization procedures do not allow repeated blood sampling. We have developed a procedure which allows arterial sampling on repeated occasions in the same animal. PROCEDURES: Eleven male Wistar rats were two times catheterized via a superficial branch of a femoral artery and scanned with [(11)C]MPDX and blood sampling...
October 2016: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
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