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radiotracer Investigation of the Effect of Impeller Type on Mixing in Industrial Process Simulator

Journal of Applied Mathematics and Physics 2018年第3期6卷 468-474页

作者： Simon Yao Adzaklo Christian Priesley Kofi Dagadu Ishmael Iddisah Mumuni Patience Adwoa Serwah Adu Hannah Asamoah Affum Godfred Kofi Appiah Alexander Coleman National Nuclear Research Institute Ghana Atomic Energy Commission Legon-Accra Ghana

radiotracer technology has been applied in industry for the investigation of process performance, online monitoring of conditions of process units, troubleshooting and diagnosing anomalies including mixing conditions in continuous stirred tank reactors. In this study, radiotracer methodology was used to carry out investigation on a laboratory water flow rig which serves as simulator of industrial processes. The aims of the investigation were to assess: i) the effect of impeller type on mixing and ii) the fluid dynamics of the water in the vessels since both the vessels and the impellers were redesigned and reconstructed. Four similar vessels in series circuit with different impeller configurations were investigated. Tank 1 has 1 axial impeller, Tank 2 has 2 axial impellers, Tank 3 has 2 radial impellers and Tank 4 has no impeller. The data were collected by introducing 8 mCi liquid technetium-99 m at the inlet stream of the vessels and the gamma signal was detected with thallium activated NaI detector placed at the outlet of the vessels. Residence Time Distribution (RTD) curves for the outlet tracer concentration were generated from which the Mean Residence Time (MRT) and the variance were calculated by the method of moments. The extent of material mixing in the vessels was inferred from the variances and the fluid dynamics was obtained by modeling. The extent of mixing was highest in Tank 2 followed by Tank 3, and Tank 4 gave the poorest mixing. The outlet response curves were fitted with mathematical models using DTS pro and “RTD Software”. The best fit for Tanks 2, 3 and 4 was Perfect Mixers in Series with Exchange (PMSE) model while Perfect Mixers in Series with Recycle (PMSR) model best described the fluid dynamics of the material in Tank 1.

关键词： Axial Impellers Mixing Radial radiotracer

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Evaluation of 64Cu-DOTA- and 64Cu-CBTE2A-Galectin-3 Peptide as a PET radiotracer for breast Carcinoma

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Advances in Molecular Imaging 2011年第1期1卷 1-11页

作者： Senthil R. Kumar Susan L. Deutscher University of Missouri-Columbia School of Medicine

Galectin-3 (Gal-3) is a β-galactosidase binding protein that modulates various cellular processes including cell adhesion, and metastasis. We evaluated the tumor targeting and imaging properties of a galectin-3 binding peptide originally selected from bacteriophage display, in a mouse model of human breast carcinoma expressing galectin-3. A galectin-3 binding peptide, ANTPCGPYTHDCPVKR, was synthesized with a Gly-Ser-Gly (GSG) spacer and 1,4,7,10, tetraazacyclododecane-N,N’,N’’,N’’’-tetracetic acid (DOTA) or 4,11-bis(carboxymethyl)-1,4,8,11 tetrazabicyclo[6.6.2]hexadecane 4,11-diacetic acid (CB-TE2A), and radiolabeled with 64Cu. The synthesized peptides 64Cu-DO3A-(GSG)-ANTPCGPYTHDCPVKR (64Cu-DO3A- pep) and 64Cu-CB-TE2A-(GSG)-ANTPCGPYTHDCPVKR(64Cu-CB-TE2A-pep) demonstrated an IC50 value of 97 ± 6.7 nM and 130 ± 10.2 nM, respectively, to cultured MDA-MB-435 breast carcinoma cells in vitro in a competitive displacement binding study. The tumor tissue uptake in SCID mice bearing MDA-MB-435 tumors was 1.2 ± 0.18 %ID/g (64Cu-DO3A-pep) and 0.85 ± 0.0.9 %ID/g (64Cu-CB-TE2A-pep) at 30 min, respectively. While liver retention was moderate with both radiolabeled peptides the kidney retention was observed to be high. Radiation dose delivered to the tumor was estimated to be 42 mGy/mCi and 129 mGy/ mCi with CB-TE2A and DO3A peptides, respectively. Imaging studies demonstrated tumor uptake with both 64Cu-DO3A- and 64Cu-CB-TE2A-(GSG)-ANTPCGPYTHDCPVKR after 2 h post injection. These studies suggest that gal-3 binding peptide could be developed into a PET imaging agent for galectin-3-expressing breast tumors.

关键词： Galectin-3 Breast Cancer PET Imaging Peptide radiotracer

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Development of ^(18)F-labeled radiotracers for neuroreceptor imaging with positron emission tomography

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Neuroscience Bulletin 2014年第5期30卷 777-811页

作者： Peter Brust Jrg van den Hoff Jrg Steinbach Helmholtz-Zentrum Dresden-Rossendorf Institute of Radiopharmaceutical Cancer ResearchPermoserstrasse 15Leipzig04318Germany

Positron emission tomography （PET） is an in vivo molecular imaging tool which is widely used in nuclear medicine for early diagnosis and treatment follow-up of many brain diseases. PET uses biomolecules as probes which are labeled with radionuclides of short half-lives, synthesized prior to the imaging studies. These probes are called radiotracers. Fluorine-18 is a radionuclide routinely used in the radiolabeling of neuroreceptor ligands for PET because of its favorable half-life of 109.8 min. The delivery of such radiotracers into the brain provides images of transport, metabolic, and neurotransmission processes on the molecular level. After a short introduction into the principles of PET, this review mainly focuses on the strategy of radiotracer development bridging from basic science to biomedical application. Successful radiotracer design as described here provides molecular probes which not only are useful for imaging of human brain diseases, but also allow molecular neuroreceptor imaging studies in various small-animal models of disease, including genetically- engineered animals. Furthermore, they provide a powerful tool for in vivo pharmacology during the process of pre-clinical drug development to identify new drug targets, to investigate pathophysiology, to discover potential drug candidates, and to evaluate the pharmacokinetics and pharmacodynamics of drugs in vivo.

关键词： Alzheimer's disease autoradiography blood-brain barrier brain tumor cholinergic system kinetic modeling metabolism molecular imaging neurodegeneration positron emission tomography precursor psychiatric disorder radiotracer sigma receptor

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Interventional Radionuclide Therapy of Hepatocellular Carcinoma： Assessment of Intratumoral Retention of HPMA Copolymers

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Chemical Research in Chinese Universities 2013年第1期29卷 183-188页

作者： YUAN Jian-chao MIAO Cheng-ping ZENG Xian-wu GUO Hong-yun WANG Xiao-qi LIAO Shi-qi XIE Xiao-li Key Laboratory of Eco-environment-related Polymer Materials Ministry of Education Key Laboratory of Polymer Materials of Gansu Province College of Chemistry and Chemical Engineering Department of Nuclear Medicine Gansu Academy of Medical Sciences & Gansu Provincial Tumor Hospital Lanzhou 730050 P. R. China

To develop new radiopharmaceuticals for the interventional radionuclide therapy of recurrent hepatocellular carcinoma, poly（HPMA）-APMA-DTPA[HPMA=N-（2-hydroxypropyl） methacrylamide; APMA=N-（3-aminopropyl）methacrylamide; DTPA=diethylenetriaminepentaacetic acidl was synthesized by free radical precipitation polymerization in acetone/dimethylsulfoxide with N,N＇-azobis（isobutyronitrile） as the initiator. The copolymers were characterized with nuclear magnetic resonance（NMR） spectroscopy and gel permeation chromatography（GPC, Mn=2.2xl04, Mw/Mn=l.38）. Subsequently, poly（HPMA）-APMA-DTPA was conjugated with 99mTC radionuclide. Prolonged retention of poly（HPMA）-APMA-DTPA conjugate within the tumor tissues was demonstrated by single-photon emission computed tomography computed tomography（SPECT-CT） at 1, 2, 4 and 24 h following intra-tumoral injection of the conjugate to hepatocellular carcinoma xenografts in mice. DTPA-99mTc was also synthesized and characterized for comparison. The data suggest that the poly（HPMA）-APMA-DTPA conjugates might be useful for the interventional radionuclide therapy of recurrent hepatocellular carcinoma in humans.

关键词： Hepatocellular carcinoma Interventional radionuclide therapy HPMA copolymer radiotracer

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Development of a potential PET probe for HDAC6 imaging in Alzheimer's disease

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Acta Pharmaceutica Sinica B 2022年第10期12卷 3891-3904页

作者： Ping Bai Prasenjit Mondal Frederick A.Bagdasarian Nisha Rani Yan Liu Ashley Gomm Darcy R.Tocci Se Hoon Choi Hsiao-Ying Wey Rudolph E.Tanzi Can Zhang Changning Wang Athinoula A.Martinos Center for Biomedical Imaging Department of RadiologyMassachusetts General HospitalHarvard Medical SchoolCharlestownMA 02129USA Genetics and Aging Research Unit McCance Center for Brain HealthMassGeneral Institute for Neurodegenerative DiseaseDepartment of NeurologyMassachusetts General HospitalHarvard Medical SchoolCharlestownMA 02129USA

Although the epigenetic regulatory protein histone deacetylase 6(HDAC6)has been recently implicated in the etiology of Alzheimer’s disease(AD),little is known about the role of HDAC6 in the etiopathogenesis of AD and whether HDAC6 can be a potential therapeutic target for ***,we performed positron emission tomography(PET)imaging in combination with histopathological analysis to better understand the underlying pathomechanisms of HDAC6 in *** first developed[^(18)F]PB118 which was demonstrated as a valid HDAC6 radioligand with excellent brain penetration and high specificity to *** studies of[^(18)F]PB118 in 5xFAD mice showed significantly increased radioactivity in the brain compared to WT animals,with more pronounced changes identified in the cortex and *** translatability of this radiotracer for AD in a potential human use was supported by additional studies,including similar uptake profiles in non-human primates,an increase of HDAC6 in ADrelated human postmortem hippocampal tissues by Western blotting protein analysis,and our ex vivo histopathological analysis of HDAC6 in postmortem brain tissues of our ***,our findings show that HDAC6 may lead to AD by mechanisms that tend to affect brain regions particularly susceptible to AD through an association with amyloid pathology.

关键词： HDAC6 Alzheimer’s disease radiotracer PET imaging Epigenetic

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Tumor targeting of HPMA copolymer conjugates containing sulfadiazine groups

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Chinese Chemical Letters 2012年第7期23卷 875-878页

作者： Jian Chao Yuan Xiao Li Xie Xian Wu Zeng Hong Yun Guo Cheng Ping Miao Key Laboratory of Eco-Environment-Related Polymer Materials of Ministry of Education Key Laboratory of Polymer Materials of Gansu ProvinceCollege of Chemistry&Chemical EngineeringNorthwest Normal UniversityLanzhou 730070China Department of Nuclear Medicine Gansu Academy of Medical Sciences&Gansu Provincial Tumor HospitalLanzhou 730050China

To develop new tumor targeting macromolecular conjugates,poly（HPMA）-SD-APMA-DTPA（HPMA：N-（2-hydroxypropyl）- methacrylamide;APMA：N-（3-ammopropyl）methacrylamide;DTPA：diethylenetriaminepentaacetic acid;SD：sulfadiazine） was synthesized and *** poly（HPMA）-SD-DTPA conjugates were radiolabeled with the radionuclide ^（99m）Tc and tested for uptake by cultured H22 cells in ***-^（99m）Tc（radiotracer 1） and poly（HPMA）-DTPA-^（99m）Tc（radiotracer 2） were also synthesized and characterized for *** uptake of poly（HPMA）-SD-DTPA-^（99m）Tc（radiotracer 3,34.76%） was significantly higher than that of poly（HPMA）-DTPA-^（99m）Tc（16.40%）,indicating that uptake of the poly（HPMA）-SD-DTPA-^（99m）T was active *** uptake of poly（HPMA）-DTPA-^（99m）Tc was significantly higher than that of DTPA-^（99m）Tc（2.98%）, suggesting that uptake of the poly（HPMA）-DTPA-^（99m）T was passive *** data suggest that the poly（HPMA）-SDAPMA -DTPA conjugates might be useful as tumor targeting macromolecular conjugates.

关键词： Tumor targeting HepatoceUular carcinoma HPMA copolymer conjugates radiotracer

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Synthesis and characterization of the two enantiomers of a chiral sigma-1 receptor radioligand:(S)-(+)-and(R)-(-)-[^(18)F]FBFP

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Chinese Chemical Letters 2022年第7期33卷 3543-3548页

作者： Tao Wang Ying Zhang Xiaojun Zhang Leyuan Chen Mingqiang Zheng Jinming Zhang Peter Brust Winnie Deuther-Conrad Yiyun Huang Hongmei Jia Key Laboratory of Radiopharmaceuticals(Beijing Normal University) Ministry of EducationCollege of ChemistryBeijing Normal UniversityBeijing 100875China Nuclear Medicine Department The First Medical Center of Chinese PLA General HospitalBeijing 100853China Institute of Radiation Medicine Peking Union Medical College&Chinese Academy of Medical SciencesTianjin 300192China Yale PET Center Department of Radiology and Biomedical ImagingYale University School of MedicineNew HavenCT 06520-8048United States Helmholtz-Zentrum Dresden-Rossendorf Institute of Radiopharmaceutical Cancer ResearchDepartment of NeuroradiopharmaceuticalsLeipzig 04318Germany The Lübeck Institute of Experimental Dermatology University Medical Center Schleswig-HolsteinLubeck 23562.Germany

Racemic[^(18)F]FBFP([^(18)F]1)proved to be a potentσ_(1) receptor radiotracer with superior imaging *** pure enantiomers of unlabeled compounds(S)-and(R)-1 and the corresponding iodonium ylide precursors were synthesized and *** two enantiomers(S)-1 and(R)-1 exhibited comparable high affinity forσ_(1) receptors and selectivity overσ_(2) *** Ca^(2+) fluorescence assay indicated that(R)-1 behaved as an antagonist and(S)-1 as an agonist forσ_(1) *** ^(18)F-labeled enantiomers(S)-and(R)-[^(18)F]1 were obtained in>99%enantiomeric purity from the corresponding enantiopure iodonium ylide precursors with radiochemical yield of 24.4%±2.6%and molar activity of 86–214 GBq/μ*** ICR mice both(S)-and(R)-[^(18)F]1displayed comparable high brain uptake,brain-to-blood ratio,in vivo stability and binding specificity in the brain and peripheral *** micro-positron emission tomography(PET)imaging studies in rats,(S)-[^(18)F]1 exhibited faster clearance from the brain than(R)-[^(18)F]1,indicating different brain kinetics of the two ***(S)-and(R)-[^(18)F]1 warrant further evaluation in primates to translate a single enantiomer with more suitable kinetics for imaging theσ_(1) receptors in humans.

关键词： σ_(1)receptor Enantiomer radiotracer Positron emission tomography Fluorine-18

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Positron-emission tomography for hepatocellular carcinoma:Current status and future prospects

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World Journal of Gastroenterology 2019年第32期25卷 4682-4695页

作者： Ren-Cai Lu Bo She Wen-Tao Gao Yun-Hai Ji Dong-Dong Xu Quan-Shi Wang Shao-Bo Wang PET-CT Center the First People’s Hospital of Yunnan ProvinceKunming 650032Yunnan ProvinceChina Nanfang PET Center Nanfang HospitalSouthern Medical UniversityGuangzhou 510515Guangdong ProvinceChina Yunnan Key Laboratory of Primate Biomedical Research Institute of Primate Translational MedicineKunming University of Science and TechnologyKunming 650093Yunnan ProvinceChina

Hepatocellular carcinoma(HCC)is one of the leading causes of cancer mortality *** imaging modalities provide important information about HCC for its clinical *** positron-emission tomography(PET)or PET-computed tomography was introduced to the oncologic setting,it has played crucial roles in detecting,distinguishing,accurately staging,and evaluating local,residual,and recurrent *** imaging visualizes tissue metabolic information that is closely associated with *** PET imaging and dual-tracer have emerged as complementary techniques that aid in various aspects of HCC *** advent of new radiotracers and the development of immuno-PET and PET-magnetic resonance imaging have improved the ability to detect lesions and have made great progress in treatment *** current PET diagnostic capabilities for HCC and the supplementary techniques are reviewed herein.

关键词： Hepatocellular carcinoma Positron-emission tomography radiotracer Immuno-positron emission tomography

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Application of Positron Emission Tomography Molecular Probes in Hepatocellular Carcinoma Biological Imaging

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Chinese Medical Sciences Journal 2011年第2期26卷 113-118页

作者： Ting-ting He Jia-he Tian Department of Nuclear Medicine General Hospital of the Chinese People＇s Liberation Army Beijing 100853 China

Biological behavior is a hot issue in hepatocellular carcinoma (HCC) study. Positron emis-sion tomography (PET), a biological imaging technique, has been widely applied in many types of tumors. It is capable of noninvasive detection of biological behavior. Different radiotracers provide different information of HCC, including glucose/lipid metabolism, DNA synthesis, and apoptosis. In addition, radiotracer uptake relates to biological and clinical prognostic markers. In this article we review the application of several existing and novel radiotracers in PET in HCC study.

关键词： hepatocellular carcinoma radiotracer positron emission tomography bio-logical behavior

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