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Publisher: Elsevier   (Total: 3161 journals)

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Showing 1 - 200 of 3161 Journals sorted alphabetically
A Practical Logic of Cognitive Systems     Full-text available via subscription   (Followers: 9)
AASRI Procedia     Open Access   (Followers: 15)
Academic Pediatrics     Hybrid Journal   (Followers: 33, SJR: 1.655, CiteScore: 2)
Academic Radiology     Hybrid Journal   (Followers: 23, SJR: 1.015, CiteScore: 2)
Accident Analysis & Prevention     Partially Free   (Followers: 94, SJR: 1.462, CiteScore: 3)
Accounting Forum     Hybrid Journal   (Followers: 25, SJR: 0.932, CiteScore: 2)
Accounting, Organizations and Society     Hybrid Journal   (Followers: 34, SJR: 1.771, CiteScore: 3)
Achievements in the Life Sciences     Open Access   (Followers: 5)
Acta Anaesthesiologica Taiwanica     Open Access   (Followers: 7)
Acta Astronautica     Hybrid Journal   (Followers: 411, SJR: 0.758, CiteScore: 2)
Acta Automatica Sinica     Full-text available via subscription   (Followers: 2)
Acta Biomaterialia     Hybrid Journal   (Followers: 27, SJR: 1.967, CiteScore: 7)
Acta Colombiana de Cuidado Intensivo     Full-text available via subscription   (Followers: 2)
Acta de Investigación Psicológica     Open Access   (Followers: 3)
Acta Ecologica Sinica     Open Access   (Followers: 10, SJR: 0.18, CiteScore: 1)
Acta Haematologica Polonica     Free   (Followers: 1, SJR: 0.128, CiteScore: 0)
Acta Histochemica     Hybrid Journal   (Followers: 3, SJR: 0.661, CiteScore: 2)
Acta Materialia     Hybrid Journal   (Followers: 250, SJR: 3.263, CiteScore: 6)
Acta Mathematica Scientia     Full-text available via subscription   (Followers: 5, SJR: 0.504, CiteScore: 1)
Acta Mechanica Solida Sinica     Full-text available via subscription   (Followers: 9, SJR: 0.542, CiteScore: 1)
Acta Oecologica     Hybrid Journal   (Followers: 12, SJR: 0.834, CiteScore: 2)
Acta Otorrinolaringologica (English Edition)     Full-text available via subscription  
Acta Otorrinolaringológica Española     Full-text available via subscription   (Followers: 2, SJR: 0.307, CiteScore: 0)
Acta Pharmaceutica Sinica B     Open Access   (Followers: 1, SJR: 1.793, CiteScore: 6)
Acta Poética     Open Access   (Followers: 4, SJR: 0.101, CiteScore: 0)
Acta Psychologica     Hybrid Journal   (Followers: 27, SJR: 1.331, CiteScore: 2)
Acta Sociológica     Open Access   (Followers: 1)
Acta Tropica     Hybrid Journal   (Followers: 6, SJR: 1.052, CiteScore: 2)
Acta Urológica Portuguesa     Open Access  
Actas Dermo-Sifiliograficas     Full-text available via subscription   (Followers: 3, SJR: 0.374, CiteScore: 1)
Actas Dermo-Sifiliográficas (English Edition)     Full-text available via subscription   (Followers: 2)
Actas Urológicas Españolas     Full-text available via subscription   (Followers: 3, SJR: 0.344, CiteScore: 1)
Actas Urológicas Españolas (English Edition)     Full-text available via subscription   (Followers: 1)
Actualites Pharmaceutiques     Full-text available via subscription   (Followers: 6, SJR: 0.19, CiteScore: 0)
Actualites Pharmaceutiques Hospitalieres     Full-text available via subscription   (Followers: 3)
Acupuncture and Related Therapies     Hybrid Journal   (Followers: 6)
Acute Pain     Full-text available via subscription   (Followers: 14, SJR: 2.671, CiteScore: 5)
Ad Hoc Networks     Hybrid Journal   (Followers: 11, SJR: 0.53, CiteScore: 4)
Addictive Behaviors     Hybrid Journal   (Followers: 16, SJR: 1.29, CiteScore: 3)
Addictive Behaviors Reports     Open Access   (Followers: 8, SJR: 0.755, CiteScore: 2)
Additive Manufacturing     Hybrid Journal   (Followers: 9, SJR: 2.611, CiteScore: 8)
Additives for Polymers     Full-text available via subscription   (Followers: 22)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 147, SJR: 4.09, CiteScore: 13)
Advanced Engineering Informatics     Hybrid Journal   (Followers: 11, SJR: 1.167, CiteScore: 4)
Advanced Powder Technology     Hybrid Journal   (Followers: 16, SJR: 0.694, CiteScore: 3)
Advances in Accounting     Hybrid Journal   (Followers: 8, SJR: 0.277, CiteScore: 1)
Advances in Agronomy     Full-text available via subscription   (Followers: 12, SJR: 2.384, CiteScore: 5)
Advances in Anesthesia     Full-text available via subscription   (Followers: 28, SJR: 0.126, CiteScore: 0)
Advances in Antiviral Drug Design     Full-text available via subscription   (Followers: 2)
Advances in Applied Mathematics     Full-text available via subscription   (Followers: 10, SJR: 0.992, CiteScore: 1)
Advances in Applied Mechanics     Full-text available via subscription   (Followers: 11, SJR: 1.551, CiteScore: 4)
Advances in Applied Microbiology     Full-text available via subscription   (Followers: 22, SJR: 2.089, CiteScore: 5)
Advances In Atomic, Molecular, and Optical Physics     Full-text available via subscription   (Followers: 14, SJR: 0.572, CiteScore: 2)
Advances in Biological Regulation     Hybrid Journal   (Followers: 4, SJR: 2.61, CiteScore: 7)
Advances in Botanical Research     Full-text available via subscription   (Followers: 2, SJR: 0.686, CiteScore: 2)
Advances in Cancer Research     Full-text available via subscription   (Followers: 31, SJR: 3.043, CiteScore: 6)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 8, SJR: 1.453, CiteScore: 2)
Advances in Catalysis     Full-text available via subscription   (Followers: 5, SJR: 1.992, CiteScore: 5)
Advances in Cell Aging and Gerontology     Full-text available via subscription   (Followers: 3)
Advances in Cellular and Molecular Biology of Membranes and Organelles     Full-text available via subscription   (Followers: 12)
Advances in Chemical Engineering     Full-text available via subscription   (Followers: 27, SJR: 0.156, CiteScore: 1)
Advances in Child Development and Behavior     Full-text available via subscription   (Followers: 10, SJR: 0.713, CiteScore: 1)
Advances in Chronic Kidney Disease     Full-text available via subscription   (Followers: 10, SJR: 1.316, CiteScore: 2)
Advances in Clinical Chemistry     Full-text available via subscription   (Followers: 29, SJR: 1.562, CiteScore: 3)
Advances in Colloid and Interface Science     Full-text available via subscription   (Followers: 19, SJR: 1.977, CiteScore: 8)
Advances in Computers     Full-text available via subscription   (Followers: 14, SJR: 0.205, CiteScore: 1)
Advances in Dermatology     Full-text available via subscription   (Followers: 15)
Advances in Developmental Biology     Full-text available via subscription   (Followers: 11)
Advances in Digestive Medicine     Open Access   (Followers: 9)
Advances in DNA Sequence-Specific Agents     Full-text available via subscription   (Followers: 5)
Advances in Drug Research     Full-text available via subscription   (Followers: 24)
Advances in Ecological Research     Full-text available via subscription   (Followers: 44, SJR: 2.524, CiteScore: 4)
Advances in Engineering Software     Hybrid Journal   (Followers: 28, SJR: 1.159, CiteScore: 4)
Advances in Experimental Biology     Full-text available via subscription   (Followers: 7)
Advances in Experimental Social Psychology     Full-text available via subscription   (Followers: 44, SJR: 5.39, CiteScore: 8)
Advances in Exploration Geophysics     Full-text available via subscription   (Followers: 1)
Advances in Fluorine Science     Full-text available via subscription   (Followers: 9)
Advances in Food and Nutrition Research     Full-text available via subscription   (Followers: 56, SJR: 0.591, CiteScore: 2)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 16)
Advances in Genetics     Full-text available via subscription   (Followers: 16, SJR: 1.354, CiteScore: 4)
Advances in Genome Biology     Full-text available via subscription   (Followers: 8, SJR: 12.74, CiteScore: 13)
Advances in Geophysics     Full-text available via subscription   (Followers: 6, SJR: 1.193, CiteScore: 3)
Advances in Heat Transfer     Full-text available via subscription   (Followers: 21, SJR: 0.368, CiteScore: 1)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 12, SJR: 0.749, CiteScore: 3)
Advances in Human Factors/Ergonomics     Full-text available via subscription   (Followers: 23)
Advances in Imaging and Electron Physics     Full-text available via subscription   (Followers: 2, SJR: 0.193, CiteScore: 0)
Advances in Immunology     Full-text available via subscription   (Followers: 36, SJR: 4.433, CiteScore: 6)
Advances in Inorganic Chemistry     Full-text available via subscription   (Followers: 8, SJR: 1.163, CiteScore: 2)
Advances in Insect Physiology     Full-text available via subscription   (Followers: 2, SJR: 1.938, CiteScore: 3)
Advances in Integrative Medicine     Hybrid Journal   (Followers: 6, SJR: 0.176, CiteScore: 0)
Advances in Intl. Accounting     Full-text available via subscription   (Followers: 3)
Advances in Life Course Research     Hybrid Journal   (Followers: 8, SJR: 0.682, CiteScore: 2)
Advances in Lipobiology     Full-text available via subscription   (Followers: 1)
Advances in Magnetic and Optical Resonance     Full-text available via subscription   (Followers: 9)
Advances in Marine Biology     Full-text available via subscription   (Followers: 16, SJR: 0.88, CiteScore: 2)
Advances in Mathematics     Full-text available via subscription   (Followers: 11, SJR: 3.027, CiteScore: 2)
Advances in Medical Sciences     Hybrid Journal   (Followers: 6, SJR: 0.694, CiteScore: 2)
Advances in Medicinal Chemistry     Full-text available via subscription   (Followers: 5)
Advances in Microbial Physiology     Full-text available via subscription   (Followers: 4, SJR: 1.158, CiteScore: 3)
Advances in Molecular and Cell Biology     Full-text available via subscription   (Followers: 21)
Advances in Molecular and Cellular Endocrinology     Full-text available via subscription   (Followers: 8)
Advances in Molecular Toxicology     Full-text available via subscription   (Followers: 7, SJR: 0.182, CiteScore: 0)
Advances in Nanoporous Materials     Full-text available via subscription   (Followers: 3)
Advances in Oncobiology     Full-text available via subscription   (Followers: 1)
Advances in Organ Biology     Full-text available via subscription   (Followers: 1)
Advances in Organometallic Chemistry     Full-text available via subscription   (Followers: 17, SJR: 1.875, CiteScore: 4)
Advances in Parallel Computing     Full-text available via subscription   (Followers: 7, SJR: 0.174, CiteScore: 0)
Advances in Parasitology     Full-text available via subscription   (Followers: 5, SJR: 1.579, CiteScore: 4)
Advances in Pediatrics     Full-text available via subscription   (Followers: 24, SJR: 0.461, CiteScore: 1)
Advances in Pharmaceutical Sciences     Full-text available via subscription   (Followers: 10)
Advances in Pharmacology     Full-text available via subscription   (Followers: 16, SJR: 1.536, CiteScore: 3)
Advances in Physical Organic Chemistry     Full-text available via subscription   (Followers: 8, SJR: 0.574, CiteScore: 1)
Advances in Phytomedicine     Full-text available via subscription  
Advances in Planar Lipid Bilayers and Liposomes     Full-text available via subscription   (Followers: 3, SJR: 0.109, CiteScore: 1)
Advances in Plant Biochemistry and Molecular Biology     Full-text available via subscription   (Followers: 9)
Advances in Plant Pathology     Full-text available via subscription   (Followers: 5)
Advances in Porous Media     Full-text available via subscription   (Followers: 5)
Advances in Protein Chemistry     Full-text available via subscription   (Followers: 18)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 20, SJR: 0.791, CiteScore: 2)
Advances in Psychology     Full-text available via subscription   (Followers: 62)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 6, SJR: 0.371, CiteScore: 1)
Advances in Radiation Oncology     Open Access   (SJR: 0.263, CiteScore: 1)
Advances in Small Animal Medicine and Surgery     Hybrid Journal   (Followers: 3, SJR: 0.101, CiteScore: 0)
Advances in Space Biology and Medicine     Full-text available via subscription   (Followers: 5)
Advances in Space Research     Full-text available via subscription   (Followers: 397, SJR: 0.569, CiteScore: 2)
Advances in Structural Biology     Full-text available via subscription   (Followers: 5)
Advances in Surgery     Full-text available via subscription   (Followers: 10, SJR: 0.555, CiteScore: 2)
Advances in the Study of Behavior     Full-text available via subscription   (Followers: 31, SJR: 2.208, CiteScore: 4)
Advances in Veterinary Medicine     Full-text available via subscription   (Followers: 17)
Advances in Veterinary Science and Comparative Medicine     Full-text available via subscription   (Followers: 13)
Advances in Virus Research     Full-text available via subscription   (Followers: 5, SJR: 2.262, CiteScore: 5)
Advances in Water Resources     Hybrid Journal   (Followers: 47, SJR: 1.551, CiteScore: 3)
Aeolian Research     Hybrid Journal   (Followers: 6, SJR: 1.117, CiteScore: 3)
Aerospace Science and Technology     Hybrid Journal   (Followers: 341, SJR: 0.796, CiteScore: 3)
AEU - Intl. J. of Electronics and Communications     Hybrid Journal   (Followers: 8, SJR: 0.42, CiteScore: 2)
African J. of Emergency Medicine     Open Access   (Followers: 6, SJR: 0.296, CiteScore: 0)
Ageing Research Reviews     Hybrid Journal   (Followers: 11, SJR: 3.671, CiteScore: 9)
Aggression and Violent Behavior     Hybrid Journal   (Followers: 446, SJR: 1.238, CiteScore: 3)
Agri Gene     Hybrid Journal   (Followers: 1, SJR: 0.13, CiteScore: 0)
Agricultural and Forest Meteorology     Hybrid Journal   (Followers: 17, SJR: 1.818, CiteScore: 5)
Agricultural Systems     Hybrid Journal   (Followers: 32, SJR: 1.156, CiteScore: 4)
Agricultural Water Management     Hybrid Journal   (Followers: 44, SJR: 1.272, CiteScore: 3)
Agriculture and Agricultural Science Procedia     Open Access   (Followers: 2)
Agriculture and Natural Resources     Open Access   (Followers: 3)
Agriculture, Ecosystems & Environment     Hybrid Journal   (Followers: 57, SJR: 1.747, CiteScore: 4)
Ain Shams Engineering J.     Open Access   (Followers: 5, SJR: 0.589, CiteScore: 3)
Air Medical J.     Hybrid Journal   (Followers: 6, SJR: 0.26, CiteScore: 0)
AKCE Intl. J. of Graphs and Combinatorics     Open Access   (SJR: 0.19, CiteScore: 0)
Alcohol     Hybrid Journal   (Followers: 11, SJR: 1.153, CiteScore: 3)
Alcoholism and Drug Addiction     Open Access   (Followers: 9)
Alergologia Polska : Polish J. of Allergology     Full-text available via subscription   (Followers: 1)
Alexandria Engineering J.     Open Access   (Followers: 1, SJR: 0.604, CiteScore: 3)
Alexandria J. of Medicine     Open Access   (Followers: 1, SJR: 0.191, CiteScore: 1)
Algal Research     Partially Free   (Followers: 11, SJR: 1.142, CiteScore: 4)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 2)
Allergologia et Immunopathologia     Full-text available via subscription   (Followers: 1, SJR: 0.504, CiteScore: 1)
Allergology Intl.     Open Access   (Followers: 5, SJR: 1.148, CiteScore: 2)
Alpha Omegan     Full-text available via subscription   (SJR: 3.521, CiteScore: 6)
ALTER - European J. of Disability Research / Revue Européenne de Recherche sur le Handicap     Full-text available via subscription   (Followers: 9, SJR: 0.201, CiteScore: 1)
Alzheimer's & Dementia     Hybrid Journal   (Followers: 50, SJR: 4.66, CiteScore: 10)
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring     Open Access   (Followers: 4, SJR: 1.796, CiteScore: 4)
Alzheimer's & Dementia: Translational Research & Clinical Interventions     Open Access   (Followers: 4, SJR: 1.108, CiteScore: 3)
Ambulatory Pediatrics     Hybrid Journal   (Followers: 6)
American Heart J.     Hybrid Journal   (Followers: 50, SJR: 3.267, CiteScore: 4)
American J. of Cardiology     Hybrid Journal   (Followers: 54, SJR: 1.93, CiteScore: 3)
American J. of Emergency Medicine     Hybrid Journal   (Followers: 45, SJR: 0.604, CiteScore: 1)
American J. of Geriatric Pharmacotherapy     Full-text available via subscription   (Followers: 10)
American J. of Geriatric Psychiatry     Hybrid Journal   (Followers: 14, SJR: 1.524, CiteScore: 3)
American J. of Human Genetics     Hybrid Journal   (Followers: 34, SJR: 7.45, CiteScore: 8)
American J. of Infection Control     Hybrid Journal   (Followers: 28, SJR: 1.062, CiteScore: 2)
American J. of Kidney Diseases     Hybrid Journal   (Followers: 34, SJR: 2.973, CiteScore: 4)
American J. of Medicine     Hybrid Journal   (Followers: 46)
American J. of Medicine Supplements     Full-text available via subscription   (Followers: 3, SJR: 1.967, CiteScore: 2)
American J. of Obstetrics and Gynecology     Hybrid Journal   (Followers: 205, SJR: 2.7, CiteScore: 4)
American J. of Ophthalmology     Hybrid Journal   (Followers: 62, SJR: 3.184, CiteScore: 4)
American J. of Ophthalmology Case Reports     Open Access   (Followers: 5, SJR: 0.265, CiteScore: 0)
American J. of Orthodontics and Dentofacial Orthopedics     Full-text available via subscription   (Followers: 6, SJR: 1.289, CiteScore: 1)
American J. of Otolaryngology     Hybrid Journal   (Followers: 25, SJR: 0.59, CiteScore: 1)
American J. of Pathology     Hybrid Journal   (Followers: 27, SJR: 2.139, CiteScore: 4)
American J. of Preventive Medicine     Hybrid Journal   (Followers: 28, SJR: 2.164, CiteScore: 4)
American J. of Surgery     Hybrid Journal   (Followers: 38, SJR: 1.141, CiteScore: 2)
American J. of the Medical Sciences     Hybrid Journal   (Followers: 12, SJR: 0.767, CiteScore: 1)
Ampersand : An Intl. J. of General and Applied Linguistics     Open Access   (Followers: 6)
Anaerobe     Hybrid Journal   (Followers: 4, SJR: 1.144, CiteScore: 3)
Anaesthesia & Intensive Care Medicine     Full-text available via subscription   (Followers: 62, SJR: 0.138, CiteScore: 0)
Anaesthesia Critical Care & Pain Medicine     Full-text available via subscription   (Followers: 17, SJR: 0.411, CiteScore: 1)
Anales de Cirugia Vascular     Full-text available via subscription  
Anales de Pediatría     Full-text available via subscription   (Followers: 3, SJR: 0.277, CiteScore: 0)
Anales de Pediatría (English Edition)     Full-text available via subscription  
Anales de Pediatría Continuada     Full-text available via subscription  
Analytic Methods in Accident Research     Hybrid Journal   (Followers: 5, SJR: 4.849, CiteScore: 10)
Analytica Chimica Acta     Hybrid Journal   (Followers: 43, SJR: 1.512, CiteScore: 5)
Analytical Biochemistry     Hybrid Journal   (Followers: 177, SJR: 0.633, CiteScore: 2)
Analytical Chemistry Research     Open Access   (Followers: 11, SJR: 0.411, CiteScore: 2)
Analytical Spectroscopy Library     Full-text available via subscription   (Followers: 11)
Anesthésie & Réanimation     Full-text available via subscription   (Followers: 2)
Anesthesiology Clinics     Full-text available via subscription   (Followers: 23, SJR: 0.683, CiteScore: 2)
Angiología     Full-text available via subscription   (SJR: 0.121, CiteScore: 0)
Angiologia e Cirurgia Vascular     Open Access   (Followers: 1, SJR: 0.111, CiteScore: 0)
Animal Behaviour     Hybrid Journal   (Followers: 190, SJR: 1.58, CiteScore: 3)

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Journal Cover
Nuclear Medicine and Biology
Journal Prestige (SJR): 0.696
Citation Impact (citeScore): 2
Number of Followers: 5  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 0969-8051
Published by Elsevier Homepage  [3161 journals]
  • Issues in preclinical radiopharmaceutical research: Significance,
           relevance and reproducibility
    • Abstract: Publication date: Available online 3 September 2018Source: Nuclear Medicine and BiologyAuthor(s): Michael R. Kilbourn, Peter J.H. Scott
       
  • Assessing the feasibility of intranasal radiotracer administration for in
           brain PET imaging
    • Abstract: Publication date: Available online 30 August 2018Source: Nuclear Medicine and BiologyAuthor(s): Nisha Singh, Mattia Veronese, Jim O'Doherty, Teresa Sementa, Salvatore Bongarzone, Diana Cash, Camilla Simmons, Marco Arcolin, Paul Marsden, Antony Gee, Federico E. TurkheimerAbstractIntroductionThe development of clinically useful tracers for PET imaging is enormously challenging and expensive. The intranasal (IN) route of administration is purported to be a viable route for delivering drugs to the brain but has, as yet, not been investigated for the delivery of PET tracers. If the intranasal (IN) pathway presents a viable option, it extends the PET imaging field by increasing the number of tracers available for human use.Here we report the results of a rodent study testing the feasibility of the IN route to administer radiotracers for brain PET imaging.MethodsWe used two different, well characterised, brain penetrant radiotracers, [18F]fluorodeoxyglucose ([18F]FDG) and [18F]fallypride, and aimed to evaluate the pharmacokinetics after administration of the tracers via the intranasal route, and contrast this to intravenous administration. Image acquisition was carried out after tracer administration and arterial blood samples were collected at different time intervals, centrifuged to extract plasma and gamma counted. We hypothesised that [brain region]:[plasma] ratios would be higher via the intranasal route as there are two inputs, one directly from the nose to the brain, and another from the peripheral circulation. To assess the feasibility of using this approach clinically, we used these data to estimate radiation dosimetry in humans.ResultsContrary to our hypothesis, in case of both radiotracers, we did not see a higher ratio in the expected brain regions, except in the olfactory bulb, that is closest to the nose. It appears that the radiotracers move into the olfactory bulb region, but then do not progress further into other brain regions. Moreover, as the nasal cavity has a small surface area, the extrapolated dosimetry estimations for intranasal human imaging showed an unacceptably high level (15 mSv/MBq) of cumulative skin radiation exposure.ConclusionsTherefore, although an attractive route for brain permeation, we conclude that the intranasal route would present difficulties due to non-specific signal and radiation dosimetry considerations for brain PET imaging.
       
  • Dynamic TSPO-PET for assessing early effects of cerebral hypoxia and
           resuscitation in new born pigs
    • Abstract: Publication date: Available online 24 August 2018Source: Nuclear Medicine and BiologyAuthor(s): Charlotte de Lange, Rønnaug Solberg, Jon Erik Holtedahl, Andreas Tulipan, Jon Barlinn, William Trigg, Torild Wickstrøm, Ola Didrik Saugstad, Eirik Malinen, Mona Elisabeth RevheimAbstractIntroductionInflammation associated with microglial activation may be an early prognostic indicator of perinatal hypoxic ischemic injury, where translocator protein (TSPO) is a known inflammatory biomarker. This piglet study used dynamic TSPO-PET with [18F]GE180 to evaluate if microglial activation after global perinatal hypoxic injury could be detected.MethodsNew born anesthetized pigs (n = 14) underwent hypoxia with fraction of inspired oxygen (FiO2)0.08 until base excess -20 mmol/L and/or a mean arterial blood pressure decrease to 20 mmHg, followed by resuscitation with FiO2 0.21 or 1.0. Three piglets served as controls and one had intracranial injection of lipopolysaccharide (LPS). Whole body [18F]GE180 Positron emission tomography-computed tomography (PET-CT) was performed repeatedly up to 32 h after hypoxia and resuscitation. Volumes of interest were traced in the basal ganglia, cerebellum and liver using MRI as anatomic correlation. Standardized uptake values (SUVs) were measured at baseline and four time-points, quantifying microglial activity over time. Statistical analysis used Mann Whitney- and Wilcoxon rank test with significance value set to p 
       
  • Preliminary evaluation of a novel 18F-labeled PARP-1 ligand for PET
           imaging of PARP-1 expression in prostate cancer
    • Abstract: Publication date: Available online 24 August 2018Source: Nuclear Medicine and BiologyAuthor(s): Dong Zhou, Jinbin Xu, Cedric Mpoy, Wenhua Chu, Sung Hoon Kim, Huifangjie Li, Buck E. Rogers, John A. KatzenellenbogenAbstractIntroductionPoly (ADP-ribose) polymerase-1 (PARP-1) plays many roles in prostate cancer (PC), such as mediating DNA damage repair, transcriptional regulation and nuclear hormone receptor signaling. Because of this, PARP-1 has been targeted for therapy in PC, and non-invasive imaging of PARP-1 could help predict which patients are likely to respond to such therapy. Several PARP-1 positron emission tomography (PET) imaging agents have been developed and show promise for imaging PARP-1 expression in breast, brain, and lung cancer in small animals, but not as yet in prostate cancer. [18F]WC-DZ-F is an analogue of [18F]FluorThanatrace (FTT) and [125I]KX1, which are well-established PARP-1 ligands for measuring PARP-1 expression. Herein, we evaluated the potential of [18F]WC-DZ-F for the imaging PARP-1 expression in PC.Methods[18F]WC-DZ-F was synthesized by a two-step sequence. [18F]WC-DZ-F was evaluated by in vitro uptake studies in PC-3 cells and by in vivo biodistribution and microPET imaging using PC-3 tumor xenografts. Ex vivo autoradiography of PC-3 tumors after microPET imaging was also performed.Results[18F]WC-DZ-F has high, PARP-1-specific uptake in PC-3 cells. In the microPET imaging study, [18F]WC-DZ-F accumulated in PC-3 xenograft tumors over 2 h, and the uptake was significantly reduced by blocking with olaparib. PC-3 tumors were clearly visualized in microPET images, and the imaging results were further confirmed by autoradiography of PC-3 tumors ex vivo. In the biodistribution study [18F]WC-DZ-F washed out quickly from most tissues within 2 h, except for the liver in which the uptake was not blockable by olaparib.ConclusionsWe synthesized a novel PARP-1 radioligand, [18F]WC-DZ-F. The preliminary evaluation of [18F]WC-DZ-F indicates that it is a suitable PET imaging agent for measuring PARP-1 expression in prostate cancer and should be applicable to other types of cancers.
       
  • Synthesis and evaluation of an N-[18F]fluorodeoxyglycosyl amino acid for
           PET imaging of tumor metabolism
    • Abstract: Publication date: Available online 16 August 2018Source: Nuclear Medicine and BiologyAuthor(s): Zhifang Wu, Jingxin Ma, Anna-liisa Brownell, Hongliang Wang, Chaomin Li, Xiaxia Meng, Ling Yuan, Haiyan Liu, Sijin Li, Jun XieAbstractIntroductionThe limitations of [18F]fluorodeoxyglucose (18F]FDG), including producing false-positive or -negative results, low image contrast in brain tumor diagnosis and poor differentiation of tumor and inflammatory, necessitate the development of amino acid based radiopharmaceuticals. In the present study, a novel [18F]fluoroglycoconjugate tracer, [18F]FDGly-NH-Phe, for tumor metabolism imaging was prepared and evaluated.Methods[18F]FDGly-NH-Phe was prepared by condensing [18F]FDG with l-4-aminophenylalanine in an acidic condition, and purified with semi-preparative-high performance liquid chromatography (HPLC). The in vitro stability study was conducted in phosphate-buffered saline (PBS, pH 6.5–9.18) at room temperature (RT) and in fetal bovine serum (FBS) at 37 °C. The preliminary cellular uptake studies were performed in Hep-2 cell. The bio-distribution studies, PET/CT imaging and metabolism studies were performed and compared with [18F]FDG on ICR mice.Results[18F]FDGly-NH-Phe was derived from direct condensation of [18F]FDG with l-4-aminophenylalanine with high stability in PBS at pH of 6.5–9.18 and in FBS. The bio-distribution of [18F]FDGly-NH-Phe in normal ICR mice showed faster blood radioactivity clearance, and lower uptake in brain and heart than [18F]FDG. The performance of PET/CT imaging of [18F]FDGly-NH-Phe in the tumor models manifested excellent tumor visualization, high tumor-to-background ratios, and low accumulation in inflammatory lesions. Metabolism studies for [18F]FDGly-NH-Phe indicated high in vivo stability in plasma and urine and decomposition into [18F]FDG in the tumor microenvironment.ConclusionThe results demonstrated that [18F]FDGly-NH-Phe as a novel PET tracer showed the capability to differentiate tumor from inflammation, and the potentials for future clinical applications.
       
  • [99mTc]duramycin, a potential molecular probe for early prediction of
           tumor response after chemotherapy
    • Abstract: Publication date: Available online 9 August 2018Source: Nuclear Medicine and BiologyAuthor(s): Yi Li, Cheng Liu, Xiaoping Xu, Xiaoling Lu, Jianming Luo, Brian Gray, Koon Y. Pak, Jingyi Cheng, Yingjian ZhangAbstractObjectiveApoptosis plays a crucial role in many biological processes, especially in cancer. However, real-time monitoring of apoptosis is challenging. [99mTc]duramycin can selectively target an apoptosis biomarker: phosphatidylethanolamine (PE), which is normally located on the intracellular cell-membrane surface but redistributes onto the outer cell-membrane upon apoptosis. Therefore, 99mTc-duramycin is a potential probe for non-invasive detection of apoptosis in real-time. The aim of this study was to evaluate the value of [99mTc]duramycin for detecting early apoptotic response in tumors after chemotherapy, thus providing a tool for early prediction of curative effects in tumors.MethodsHuman breast cancer MDA-MB-468 model mice, randomly divided into two groups, were injected with cisplatin or vehicle once per day. [99mTc]duramycin imaging was performed for group 1 before treatment and 24 h after the third day of treatment to evaluate treatment response through animal single-photon emission computed tomography (SPECT/CT). Mice in group 2 were treated for 10 days consecutively, to observe treatment response by tumor volume changes. Treatment response was further demonstrated through TdT-mediated dUTP nick-end labeling (TUNEL) and cleaved caspase-3 (CC3).Results[99mTc]duramycin uptake in MDA-MB-468 tumors was significantly higher in the treatment group than the control group after as few as 3 days of cisplatin treatment (p = 0.0001), and it also increased after treatment as comparison with that before treatment (p = 0.0001). Moreover, [99mTc]duramycin uptake in tumors clearly correlated with immunohistochemistry results (TUNEL: r = 0.892, p = 0.0001, and CC3: r = 0.89, p = 0.0001). Additionally, tumor size reduction, indicating effective treatment, was not observed until the eighth day after treatment, far later than the time when diagnosis could be made through [99mTc]duramycin imaging.Conclusions[99mTc]duramycin SPECT/CT provides a non-invasive molecular imaging strategy for early detection of tumor apoptosis after chemotherapy and thus may have great potential value in the clinic.
       
  • Effects of adding an albumin binder chain on [177Lu]Lu-DOTATATE
    • Abstract: Publication date: Available online 9 August 2018Source: Nuclear Medicine and BiologyAuthor(s): Etienne Rousseau, Joseph Lau, Zhengxing Zhang, Carlos F. Uribe, Hsiou-Ting Kuo, Chengcheng Zhang, Jutta Zeisler, Nadine Colpo, Kuo-Shyan Lin, François BénardAbstractIntroduction[177Lu]Lu-DOTATATE peptide receptor radionuclide therapy is used for treatment of neuroendocrine tumours. We investigated whether prolonging blood residence time of [177Lu]Lu-DOTATATE with albumin binders could increase tumour accumulation and tumour-to-kidney ratios for improved therapeutic efficacy.MethodsDOTATATE and its derivatives with an albumin-binder motif (GluAB-DOTATATE and AspAB-DOTATATE) were prepared by solid-phase peptide synthesis. Binding affinities of the Lu-labeled peptides for human somatostatin receptor 2 (SSTR2) were measured with membrane competition binding assays. Compounds were radiolabeled with [177Lu]LuCl3 and purified by HPLC. SPECT imaging and biodistribution studies (1, 4, 24, 72, and 120 h) were performed in immunodeficient mice bearing AR42J pancreatic tumour xenografts.ResultsGluAB-DOTATATE and AspAB-DOTATATE were synthesized in 18.8% and 14.3% yields, while Lu-GluAB-DOTATATE and Lu-AspAB-DOTATATE were obtained in 86.5% and 50.0% yields, respectively. The compounds exhibited nanomolar binding affinity (Ki: 8.72–8.95 nM) for SSTR2. The 177Lu-labeled peptides were obtained in non-decay-corrected isolated yields of ≥41%, with>96% radiochemical purity, and molar activities in the range of 314–497 GBq/μmol. In vivo, [177Lu]Lu-GluAB-DOTATATE and [177Lu]Lu-AspAB-DOTATATE had significantly higher blood activity at 1, 4 and 24 h compared to [177Lu]Lu-DOTATATE. Tumour uptake of [177Lu]Lu-DOTATATE was 21.35 ± 5.90%ID/g at 1 h and decreased to 10.10 ± 5.78%ID/g at 120 h. For [177Lu]Lu-GluAB-DOTATATE tumour uptake increased from 21.89 ± 6.86%ID/g at 1 h to 24.44 ± 5.84%ID/g at 4 h, before decreasing to 12.02 ± 1.84%ID/g at 120 h. For [177Lu]Lu-AspAB-DOTATATE tumour uptake was 11.12 ± 3.18%ID/g at 1 h, 18.41 ± 4.36%ID/g at 24 h, and decreased to 16.90 ± 8.97%ID/g at 120 h. Renal uptake was 7.49 ± 1.62%ID/g for [177Lu]Lu-DOTATATE, 31.14 ± 7.06%ID/g for [177Lu]Lu-GluAB-DOTATATE, and 28.82 ± 13.82%ID/g for [177Lu]Lu-AspAB-DOTATATE at 1 h and decreased thereafter.ConclusionThe addition of albumin binder motifs to [177Lu]Lu-DOTATATE enhanced mean residence time in blood. Increased tumour uptake was observed for [177Lu]Lu-AspAB-DOTATATE compared to [177Lu]Lu-DOTATATE at later time points, but its higher kidney uptake diminished the therapeutic index.
       
  • One-pot enzymatic synthesis of L-[3-11C]lactate for pharmacokinetic
           analysis of lactate metabolism in rat brain
    • Abstract: Publication date: Available online 7 July 2018Source: Nuclear Medicine and BiologyAuthor(s): Takashi Temma, Hidekazu Kawashima, Naoya Kondo, Makoto Yamazaki, Kazuhiro Koshino, Hidehiro IidaAbstractIntroductionLactate could serve as an energy source and signaling molecule in the brain, although there is insufficient in vivo evidence to support this possibility. Here we aimed to use a one-pot enzymatic synthetic procedure to synthesize L-[3-11C]lactate that can be used to evaluate chemical forms in the blood after intravenous administration, and as a probe for pharmacokinetic analysis of lactate metabolism in in vivo positron emission tomography (PET) scans with normal and fasted rats.MethodsRacemic [3-11C]alanine obtained from 11C-methylation of a precursor and deprotection was reacted with an enzyme mixture consisting of alanine racemase, D-amino acid oxidase, catalase, and lactate dehydrogenase to yield L-[3-11C]lactate via [3-11C]pyruvate. The optical purity was measured by HPLC. Radioactive chemical forms in the arterial blood of Sprague Dawley rats with or without insulin pretreatment were evaluated by HPLC 10 min after bolus intravenous injection of L-[3-11C]lactate. PET scans were performed on normal and fasted rats administered with L-[3-11C]lactate.ResultsL-[3-11C]lactate was synthesized within 50 min and had decay corrected radiochemical yield, radiochemical purity, and optical purity of 13.4%,> 95%, and> 99%, respectively. The blood radioactivity peaked immediately after L-[3-11C]lactate injection, rapidly decreased to the minimum value within 90 sec, and slowly cleared thereafter. HPLC analysis of blood samples revealed the presence of [11C]glucose (78.9%) and L-[3-11C]lactate (12.1%) 10 min after administration of L-[3-11C]lactate. Insulin pretreatment partly inhibited glyconeogenesis conversion leading to 55.4% as [11C]glucose and 38.9% as L-[3-11C]lactate simultaneously. PET analysis showed a higher SUV in the brain tissue of fasted rats relative to non-fasted rats.ConclusionsWe successfully synthesized L-[3-11C]lactate in a one-pot enzymatic synthetic procedure and showed rapid metabolic conversion of L-[3-11C]lactate to [11C]glucose in the blood. PET analysis of L-[3-11C]lactate indicated the possible presence of active lactate usage in rat brains in vivo.
       
  • Preclinical study of an 18F-labeled glutamine derivative for
           Cancer imaging
    • Abstract: Publication date: Available online 6 July 2018Source: Nuclear Medicine and BiologyAuthor(s): Cong Li, Hui Liu, Dongban Duan, Zhenhan Zhou, Zhibo LiuAbstractIntroductionThe emerging evidence that demonstrated the extra-demand of glutamine for cancer surviving strongly called for the development of PET tracer for imaging glutamine uptake in cancer. In this work, [18F]Gln-BF3 as a natural glutamine derivative was synthesized to explore its potential application of imaging glutamine uptake for cancer diagnosis.Methods[18F]Gln-BF3 was prepared by deprotection of purified precursor trityl-Gln-BF3 (amide bond protected with triphenylmethyl group) using TFA and radiolabeled using 18F19F isotope exchange protocol. PET imaging and biodistribution studies were conducted in Balb/c mice bearing 4 T1 xenograft.ResultsGln-BF3 was identified with HRMS ([M-H]− = 169.0765). [18F]Gln-BF3 was radiolabeled in high radiochemical yield (RCY > 25%) and characterized with Radio-HPLC-MS. Preliminary PET imaging showed the radioactivity was fast cleared from muscle tissue and excreted mainly via the renal pathway. PET study demonstrated that uptake of [18F]Gln-BF3 in 4 T1 xenografts was significant. The biodistribution results of [18F]Gln-BF3 in mice bearing 4 T1 xenograft indicate a tumor-to-muscle ratio of 2.58 ± 0.64 (n = 4) and a 6.29 ± 0.42%ID/g (n = 4) uptake in tumor at 45 min post injection.Conclusion[18F]Gln-BF3 was radiolabeled in a “kit-like” manner and showed notable and tumor-selective uptake in tumor-bearing animal models, suggesting that this new strategy of radiolabeling amino acid provided a promising solution for the future development of glutamine-derived PET tracers.
       
  • Improving metabolic stability of fluorine-18 labeled verapamil analogs
    • Abstract: Publication date: Available online 5 July 2018Source: Nuclear Medicine and BiologyAuthor(s): Renske M. Raaphorst, Gert Luurtsema, Cindy J. Schokker, Khaled A. Attia, Robert C. Schuit, Philip H. Elsinga, Adriaan A. Lammertsma, Albert D. WindhorstAbstractIntroductionFluorine-18 labeled positron emission tomography (PET) tracers were developed to obtain more insight into the function of P-glycoprotein (P-gp) in relation to various conditions. They allow research in facilities without a cyclotron as they can be transported with a half-life of 110 min. As the metabolic stability of previously reported tracers [18F]1 and [18F]2 was poor, the purpose of this study was to improve this stability using deuterium substitution, creating verapamil analogs [18F]1-d4, [18F]2-d4, [18F]3-d3 and [18F]3-d7.MethodsThe following deuterium containing tracers were synthesized and evaluated in mice and rats: [18F]1-d4, [18F]2-d4, [18F]3-d3 and [18F]3-d7.ResultsThe deuterated analogs [18F]2-d4, [18F]3-d3 and [18F]3-d7 showed increased metabolic stability compared with their non-deuterated counterparts. The increased metabolic stability of the methyl containing analogs [18F]3-d3 and [18F]3-d7 might be caused by steric hindrance for enzymes.ConclusionThe striking similar in vivo behavior of [18F]3-d7 to that of (R)-[11C]verapamil, and its improved metabolic stability compared with the other fluorine-18 labeled tracers synthesized, supports the potential clinical translation of [18F]3-d7 as a PET radiopharmaceutical for P-gp evaluation.
       
  • [18F]diphenyl sulfide derivatives for imaging serotonin
           transporter (SERT) in the brain
    • Abstract: Publication date: Available online 4 July 2018Source: Nuclear Medicine and BiologyAuthor(s): Yan Zhang, Futao Liu, Hao Xiao, Xinyue Yao, Genxun Li, Seok Rye Choi, Karl Ploessl, Zhihao Zha, Lin Zhu, Hank F. KungAbstractObjectivesSerotonin transporters (SERT) play an important role in controlling serotonin concentration in the synaptic cleft and in managing postsynaptic signal transduction. Inhibitors of SERT binding are well known as selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, sertraline, paroxetine, and escitalopram, that are commonly prescribed antidepressants. Positron emission tomography (PET) and single photon emission tomography (SPECT) imaging agents targeting SERT may be useful for studying its function and providing a tool for monitoring drug treatment.MethodsA series of novel 18F-labeled diphenyl sulfide derivatives were prepared and tested for their binding affinity. Among them, 2-((2-((dimethylamino)-methyl)-4-(2-(2-fluoroethoxy)ethoxy)phenyl)thio)aniline, 1, which showed excellent binding toward serotonin transporter (SERT) in the brain (Ki = 0.09 nM), was selected for further evaluation. An active OTs intermediate, 7, was treated with [18F]F−/K222 to provide [18F]1 in one step and in high radiochemical yields. This new SERT targeting agent was evaluated in rats by biodistribution studies and animal PET imaging studies.ResultsThe radiolabeling reaction led to the desired [18F]1. After HPLC purification no-carrier-added [18F]1 was obtained (radiochemical yield, 23–47% (n = 10,); radiochemical purity>99%; molar activity, 15–28 GBq/μmol). Biodistribution studies with [18F]1 showed good brain uptake (1.04% dose/g at 2 min post-injection), high uptake into the hypothalamus (1.55% dose/g at 30 min), and a high target-to-non-target (hypothalamus to cerebellum) ratio of 6:10 at 120 min post-injection. A PET imaging study in normal rats showed excellent uptake in the midbrain and thalamus regions known to be rich in SERT binding sites at 60 min after iv injection. Chasing experiment with escitalopram (iv, 2 mg/kg) in a rat at 60 min after iv injection caused a noticeable reduction in the regional radioactivity and the target-to-non-target ratio, suggesting binding by [18F]1 was highly specific and reversible for SERT binding sites in the brain.ConclusionsA novel diphenyl sulfide derivative, [18F]1 for SERT imaging was successfully prepared and evaluated. Results suggest that this new chemical entity is targeting SERT binding sites in the brain, and it is a suitable candidate for future commercial development.
       
  • Influence of transport line material on the molar activity of cyclotron
           produced [18F]fluoride
    • Abstract: Publication date: Available online 30 June 2018Source: Nuclear Medicine and BiologyAuthor(s): Nina Savisto, Jörgen Bergman, Jussi Aromaa, Sarita Forsback, Olli Eskola, Tapio Viljanen, Johan Rajander, Stefan Johansson, Julian Grigg, Sajinder Luthra, Olof SolinAbstractIntroductionProduction of fluorine-18–labeled radiopharmaceuticals is always associated with the varying levels of the same compound containing stable fluorine-19. In practice, this affects the molar activity (Am), defined as amount of radioactivity divided by the molar quantity (Bq/mol).We have focused on studying how the material of the transport tubing connecting the cyclotron target chamber to the synthesis device affects the concentration of fluoride in the water arriving to the reaction vessel and subsequently the Am of the fluorine-18 labeled radiopharmaceuticals produced.MethodsBatches of irradiated and non-irradiated water were analyzed for fluoride content after being transported via non-fluorinated (PEEK, PP) and fluorinated (PTFE, ETFE) tubing or using no tubing at all. Am for the [18F]fluoride was determined and compared with the Am of [18F]fluciclatide, synthesized from the same [18F]fluoride containing batches of water.ResultsSignificantly higher concentrations of fluoride were seen in irradiated water that was transported in fluorinated tubing compared to non-irradiated water transported in tubing of the same material. This elevation of fluoride concentration is presumably caused by the interaction of ionizing radiation with the fluorinated tubing used between the target chamber and hot cell. Likewise, a significant difference was seen for PEEK tubing (non-fluorinated). This could be due to the fact that fluorine containing compounds are used in the manufacture of PEEK.When using fluorinated tubing for transport of the irradiated water, the resulting fluciclatide concentrations were significantly higher compared to when using non-fluorinated tubing. No significant difference was seen between fluciclatide concentrations when PTFE or ETFE tubing was compared to each other. Using no tubing resulted in lowest fluciclatide concentration.ConclusionsFluorinated tubing is a source of stable fluoride, and Am can be increased by using non-fluorinated transport tubing. Of all the tubing materials studied PP is preferred.
       
  • Semi-automated system for concentrating 68Ga-eluate to obtain high molar
           and volume concentration of 68Ga-Radiopharmaca for preclinical
           applications
    • Abstract: Publication date: Available online 27 June 2018Source: Nuclear Medicine and BiologyAuthor(s): Erik de Blois, Rory M.S. de Zanger, Elisabeth Oehlke, Ho Sze Chan, Wouter A.P. BreemanAbstractIntroduction68Ga-radiopharmaceuticals are common in the field of Nuclear Medicine to visualize receptor-mediated processes. In contrast to straightforward labeling procedures for clinical applications, preclinical in vitro and in vivo applications are hampered for reasons like e.g. volume restriction, activity concentration, molar activity and osmolality. Therefore, we developed a semi-automatic system specifically to overcome these problems. A difficulty appeared unexpectedly, as intrinsic trace metals derived from eluate (Zn, Fe and Cu) are concentrated as well in amounts that influence radiochemical yield and thus lower molar activity.MethodsTo purify Gallium-68 and to reduce the high elution volume of a 68Ga-generator, a NaCl-based method using a column containing PS-H+ was implemented in a low volume PEEK system. Influence on reducing osmolality, acidity and the amount of PS-H+ resin (15-50 mg) was investigated. [68Ga]Ga was desorbed from the PS-H+ resin with acidified 2-5M NaCl (containing 0.05 M of HCl) and 68Ga-activity was collected. DOTA-TATE was used as a peptide model. All buffers and additives used for labeling were mixed with Chelex 100 (~1 g/50 mL) for>144h and eventually filtered using a 0.22μm filter (Millipore). Quantification of metals was performed after labeling by HPLC (UV).ResultsGallium-68 activity could be desorbed from PS-H+ cation column with 3 M NaCl, and>60% (120-180 MBq) of [68Ga]Ga was collected in 99% (ITLC), and a radiochemical purity of>95% (HPLC).ConclusionWith the here described concentration system and metal purification technique, a low activity containing 68Ga-generator can be used to label DOTA-peptide in preclinical applicable amounts>60 MBq/nmol (40-60 MBq/0.1 mL) and within 20 minutes.
       
  • Predicting response to sepantronium bromide (YM155), a survivin
           suppressant, by PET imaging with [11C]YM155
    • Abstract: Publication date: Available online 27 June 2018Source: Nuclear Medicine and BiologyAuthor(s): Keisuke Mitsuoka, Aya Kita, Yoshihiro Murakami, Kenna Shirasuna, Akihiro Noda, Kentaro Yamanaka, Naoki Kaneko, Sosuke MiyoshiAbstractIntroductionSepantronium bromide (YM155) is a survivin suppressant that induces apoptosis in tumor cells. Although YM155 induces tumor regression in various tumor types in vivo, phase I and II studies demonstrated responding and non-responding patient populations. We investigated 11C-labeled YM155 ([11C]YM155) used as a positron emission tomography (PET) tracer to assess whether tumor uptake of [11C]YM155 correlated with its anti-tumor effect, thereby allowing identification of patients who would respond to YM155 treatment.Methods(1) Uptake of YM155 was measured in 39 human cancer cell lines in vitro using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). (2) In vivo tumor uptake was assessed in xenografted mice and total body distribution was evaluated in a cynomolgus monkey using [11C]YM155 with PET/computed tomography (CT) (mice) and PET (monkey) imaging.ResultsIntracellular uptake of YM155 in human cancer cell lines correlated well with its in vitro efficacy measured by GI50 (Pearson's r = −0.5709). Similarly, in vivo studies using tumor xenografted mice showed that tumors sensitive to YM155 demonstrated robust uptake of [11C]YM155, whereas insensitive tumors demonstrated low uptake. In the monkey, the biodistribution of [11C]YM155 indicated low accumulation in lung, breast, head, and neck and was only significant in organs involved with drug clearance: i.e. liver, kidneys, and bladder.ConclusionsRobust uptake of [11C]YM155 by a tumor appears to be a positive predictive marker for a good response to YM155. The findings suggest the potential utility of PET/CT imaging with [11C]YM155 for selection of patients whose tumors are likely to respond to YM155.Advances in KnowledgeYM155 efficacy correlated closely with its in vitro intracellular uptake and uptake on [11C]YM155 PET imaging. [11C]YM155 PET may predict tumor sensitivity to YM155.Implications for Patient CareThe concept that tumor response can be accurately predicted prior to chemotherapy should be exploited to improve cancer treatment outcomes through judicious patient selection. The small molecule sepantronium bromide (YM155), a survivin suppressant, has been developed for the treatment of several cancers, including non-Hodgkin lymphoma, lung cancer, and breast cancer. The preferentially high in vitro uptake of YM155 by YM155-sensitive cancer cells and the high in vivo uptake of [11C]YM155 in YM155-sensitive tumors demonstrated by PET imaging suggest the potential utility of performing [11C]YM155 PET to allow the identification of patients with YM155-sensitive tumors.
       
  • Evaluation of a chloride-based 89Zr isolation strategy using a tributyl
           phosphate (TBP)-functionalized extraction resin
    • Abstract: Publication date: Available online 18 June 2018Source: Nuclear Medicine and BiologyAuthor(s): Stephen A. Graves, Christopher Kutyreff, Kendall E. Barrett, Reinier Hernandez, Paul A. Ellison, Steffen Happel, Eduardo Aluicio-Sarduy, Todd E. Barnhart, Robert J. Nickles, Jonathan W. EngleAbstractIntroductionThe remarkable stability of the 89Zr-DOTA complex has been shown in recent literature. The formation of this complex appears to require 89Zr-chloride as the complexation precursor rather than the more conventional 89Zr-oxalate. In this work we present a method for the direct isolation of 89Zr-chloride from irradiated natY foils.Methods89Zr, 88Zr, and 88Y were prepared by 16 MeV proton irradiation of natY foils and used for batch-extraction based equilibrium coefficient measurements for TBP and UTEVA resin. Radionuclidically pure 89Zr was prepared by 14 MeV proton-irradiation of natY foils. These foils were dissolved in concentrated HCl, trapped on columns of TBP or UTEVA resin, and 89Zr-chloride was eluted in 9 M for Zr, falling to Kd values of
       
  • Establishment of a method for in-vivo SPECT/CT imaging analysis of
           111In-labeled exendin-4 pancreatic uptake in mice without the need for
           nephrectomy or a secondary probe
    • Abstract: Publication date: Available online 8 June 2018Source: Nuclear Medicine and BiologyAuthor(s): Keita Hamamatsu, Hiroyuki Fujimoto, Naotaka Fujita, Takaaki Murakami, Hiroyuki Kimura, Hideo Saji, Nobuya InagakiAbstractIntroductionRadiolabeled exendin derivatives have been developed to visualize and quantify pancreatic beta cells. However, there are currently no established methods for analyzing in-vivo SPECT/CT images to quantify probe accumulation in the pancreas in rodent models. In this study, we aimed to establish an analytical method for murine in-vivo SPECT/CT imaging.MethodsFirst, we investigated the correlation between radioactivity measured by curiemeter and uptake calculated from SPECT/CT images of pancreata harvested after probe injection. Second, ROI volume necessary for reliable estimation of pancreatic uptake value was also examined. Third, the influence of high renal uptake on analysis was investigated with SPECT/CT imaging of harvested kidneys. Fourth, we compared pancreatic uptake values and ROI volumes estimated from in-vivo SPECT/CT images of pre- and post-nephrectomy mice. Finally, we assessed the correlation between the pancreatic uptake values from in-vivo SPECT/CT image analysis and radioactivity of harvested pancreata determined with a curiemeter.ResultsRadioactivity of harvested pancreata measured by curiemeter and uptake values derived from SPECT/CT imaging of harvested pancreas showed an almost perfect correlation (r = 0.99, p 40% of the volume of the whole pancreas enabled reliable estimates of uptake (%CV 
       
 
 
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