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"small animal PET"

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...
August 9, 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
Sangeeta Ray Banerjee, Zhengping Chen, Mrudula Pullambhatla, Ala Lisok, Jian Chen, Ronnie C Mease, Martin G Pomper
(68)Ga-labeled, low-molecular-weight imaging agents that target the prostate-specific membrane antigen (PSMA) are increasingly used clinically to detect prostate and other cancers with positron emission tomography (PET). The goal of this study was to compare the pharmacokinetics of three PSMA-targeted radiotracers: (68)Ga-1, using DOTA-monoamide as the chelating agent; (68)Ga-2, containing the macrocyclic chelating agent p-SCN-Bn-NOTA; and (68)Ga-DKFZ-PSMA-11, currently in clinical trials, which uses the acyclic chelating agent, HBED-CC...
June 15, 2016: Bioconjugate Chemistry
Valerie S Honndorf, Stefan Wiehr, Anna-Maria Rolle, Julia Schmitt, Luisa Kreft, Letitia Quintanilla-Martinez, Ursula Kohlhofer, Gerald Reischl, Andreas Maurer, Karsten Boldt, Michael Schwarz, Holger Schmidt, Bernd J Pichler
UNLABELLED: The natural phytoestrogen genistein is known as protein kinase inhibitor and tumor suppressor in various types of cancers. We studied its antitumor effect in two different xenograft models using positron emission tomography (PET) in vivo combined with ex vivo histology and nuclear magnetic resonance (NMR) metabolic fingerprinting. PROCEDURES: A431 and Colo205 tumor-bearing mice were treated with vehicle or genistein (500 mg/kg/d) over a period of 12 days...
May 10, 2016: Oncotarget
Raymond R Raylman, Alexander V Stolin, Peter F Martone, Mark F Smith
Mice are the perhaps the most common species of rodents used in biomedical research, but many of the current generation of small animal PET scanners are non-optimal for imaging these small rodents due to their relatively low resolution. Consequently, a number of researchers have investigated the development of high-resolution scanners to address this need. In this investigation, the design of a novel, high-resolution system based on the dual-detector, virtual-pinhole PET concept was explored via Monte Carlo simulations...
February 2016: IEEE Transactions on Nuclear Science
Hiroshi Wakabayashi, Rudolf A Werner, Nobuyuki Hayakawa, Mehrbod S Javadi, Xinyu Chen, Ken Herrman, Steven P Rowe, Constantin Lapa, Takahiro Higuchi
: Accurate assessment of kidney function plays an essential role for optimal clinical decision-making in a variety of diseases. The major intrinsic advantages of positron emission tomography (PET) are superior spatial and temporal resolutions for quantitative tomographic renal imaging. 2-deoxy-2-(18)F-fluorodeoxysorbitol ((18)F-FDS) is an analogue of sorbitol that is reported to be freely filtered at the renal glomerulus without re-absorption at the tubule. Furthermore, it can be synthesized via simple reduction of widely available 2-deoxy-2-(18)F-fluorodeoxyglucose ((18)F-FDG)...
March 24, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Yongfeng Yang, Julien Bec, Jian Zhou, Mengxi Zhang, Martin S Judenhofer, Xiaowei Bai, Kun Di, Yibao Wu, Mercedes Rodriguez, Purushottam Dokhale, Kanai S Shah, Richard Farrell, Jinyi Qi, Simon R Cherry
UNLABELLED: We developed a prototype small-animal PET scanner based on depth-encoding detectors using dual-ended readout of small scintillator elements to produce high and uniform spatial resolution suitable for imaging the mouse brain. METHODS: The scanner consists of 16 tapered dual-ended-readout detectors arranged in a 61-mm-diameter ring. The axial field of view (FOV) is 7 mm, and the transaxial FOV is 30 mm. The scintillator arrays consist of 14 × 14 lutetium oxyorthosilicate elements, with a crystal size of 0...
July 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Yunqi Zhu, Ruili Du, Yuankai Zhu, Yehua Shen, Kai Zhang, Yao Chen, Fahuan Song, Shuang Wu, Hong Zhang, Mei Tian
UNLABELLED: Posttraumatic stress disorder (PTSD) is an anxiety disorder that occurs after exposure to a traumatic event. This study aimed to investigate the neurobiologic changes before and after exposure-based therapy by PET in a rat model of PTSD. METHODS: Serial (18)F-FDG PET imaging studies were performed under the control (tone presentation), fear-conditioning, and extinction retrieval phases. Neuroactivity marker c-Fos protein was used for immunostaining. RESULTS: Increased glucose metabolism was observed in the bilateral amygdala after fear-conditioning (P < 0...
September 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
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