Turku PET pdf/Survival strategies...¢  2006-08-08¢  14 May 2004 Turku PET...

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Transcript of Turku PET pdf/Survival strategies...¢  2006-08-08¢  14 May 2004 Turku PET...

  • 14 May 2004 Turku PET Centre/ Olof Solin

    Turku PET Centre Finland

    A Joint National Research Institute of University of Turku,

    Åbo Akademi University and Turku University Central Hospital

  • 14 May 2004 Turku PET Centre/ Olof Solin

    Turku PET Centre • A National Research Institute for PET • Staff and investigators: 98 persons • 3 cyclotrons, 4 PET scanners, 1 MRI (2004) • Facilities about 3000 m2, 16 hot cells (2004) • >30 different tracers in routine use • 80% research, 20% diagnostic service • ~100 publications / year

    http://pet.utu.fi

  • 14 May 2004 Turku PET Centre/ Olof Solin

    Facilities • Åbo Akademi University

    – Cyclotron laboratory 1973 • University of Turku

    – Radiochemistry laboratory 1978 – Medicity preclinical laboratory 1992

    • TUCH – PET-laboratory (1. PET Scanner) 1988 – O-15 cyclotron 1992

    • National PET Centre 1996 – 2nd PET Scanner 1996 – New PET-Centre building 1999 – New radiocemistry laboratory 2003 – New cyclotron 2003 – New high resolution PET 2003 – PET/CT scanner 2004

  • 14 May 2004 Turku PET Centre/ Olof Solin

    Turku PET Centre - Key Tasks

    • High quality scientific work

    • Diagnostic service for the whole country

  • 14 May 2004 Turku PET Centre/ Olof Solin

    The Research Strategy of the Turku PET Centre

    • Cellular Energy Metabolism in Health and Disease

    • Neurotransmission in Health and Disease

    • Drug Discovery and Development

  • 14 May 2004 Turku PET Centre/ Olof Solin

    Turku PET Centre Functional Organisation

    Metabolic Research Pirjo Nuutila

    Neurotransmission Research Jarmo Hietala

    Drug Research Harry Scheinin

    National scientific board

    Management group Scientific project group

    Quality Manager Pertti Lehikoinen

    (GMP QA, TUCH Pharmacy Kirsti Torniainen)

    Cyclotrons Stefan Johansson

    Automation Timo Saarinen

    Radionuclide production Sven-Johan Heselius

    F-18 Chemistry Olli Eskola

    C-11 Chemistry Kjell Någren

    O-15 Chemistry Hannu Sipilä

    Laboratory function Nina Lauren

    Radiochemistry Jörgen Bergman

    Preclinical imaging Merja Haaparanta

    PET scanning Helena Luotolinna-Lybeck

    Modelling and dosimetry Vesa Oikonen

    Information Technology Petri Numminen

    Imaging Mika Teräs

    Diagnostic service Heikki Minn

    Director Juhani Knuuti

    Executive Board

    Research projects

    Radiochemistry Research Olof Solin

  • 14 May 2004 Turku PET Centre/ Olof Solin

    Turku PET Centre organisation

    Management group • Permanent staff

    – Isotope production – Radiochemistry/Pharmacy – Imaging – Modelling

    Scientific project group • Metabolic research • Neurotransmission res. • Drug research • Targetry / Instrumentation/

    Radiochemistry /Modelling

  • 14 May 2004 Turku PET Centre/ Olof Solin

    How to do PET?

    • Radionuclide production • Substrate labeling (radiochemistry) • Quality control • PET scan • Data analysis

    – Blood radioactivity samples, metabolites – Modeling

    • Interpretation

  • 14 May 2004 Turku PET Centre/ Olof Solin

    What can be studied with PET?

    • Tissue blood flow • Tissue metabolism • The function of neurotransmitters and

    receptors • Drug pharmacokinetics and –dynamics • Gene expression

  • 14 May 2004 Turku PET Centre/ Olof Solin

    [15O] TRACERS

    [15O]H2O [15O]water Blood flow

    [15O]CO [15O]carbon monoxide Blood volume

    [15O]O2 [15O]oxygen Oxygen consumption

  • 14 May 2004 Turku PET Centre/ Olof Solin

    [18F] TRACERS

    [18F]CFT 2β-carbomethoxy-3β-(4- [18F]fluorophenyl)tropane

    Dopamine re-uptake sites in the brain

    [18F]FBPA 4-dihydroxyboryl-2-[18F]fluoro-L- phenylalanine

    Amino acid transport, boron carrier for BNCT

    [18F]FDG 2-[18F]fluoro-2-deoxy-D-glucose Glucose metabolism

    [18F]FDOPA 4,5-dihydroxy-2-[18F]fluoro-L- phenylalanine

    Pre-synaptic dopaminergic function in the brain

    [18F]FETNIM 4-[18F]fluoro-2,3-dihydroxy-1-(2- nitroimidazol-1-yl)-butanol

    Tissue hypoxia

    [18F]Fluoride Bone scintigraphy

    [18F]Fluorodopa- mine

    2-(4,5-dihydroxy-2- [18F]fluorophenyl)ethylamine

    Adrenergic innervation and tone in the heart

    [18F]Fluorometa- raminol

    (1R,2S)-2-amino-1-(4-[18F]fluoro-3- hydroxyphenyl)-1-propanol

    Adrenergic innervation in the heart

    [18F]FTHA 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid

    Fatty acid metabolism

  • 14 May 2004 Turku PET Centre/ Olof Solin

    [11C] TRACERS [11C]Acetate Oxidative metabolism in the heart [11C]Carfentanil [methyl-11C]-4-[(1-oxypropyl)phenyl-amino]-1-(2-phenylethyl)-4-

    piperidinecarboxylic acid methyl ester Opiate receptors in the brain

    [11C]CFT [N-methyl-11C]-2-β-carbomethoxy-3-β--(4-fluorophenyl)-tropane Dopamine re-uptake sites in the brain

    [11C]Choline [N-methyl-11C](2-hydroxyethyl) trimethylammonium Choline metabolism, tumours

    [11C]CIT [N-methyl-11C]-2-β-carbomethoxy-3-β--(4-iodophenyl)-tropane Dopamine re-uptake sites in the brain

    [11C]Deprenyl Monoamine oxidase B in the brain [11C]Dopa Pre-synaptic dopaminergic function in the brain

    [11C]FLB 457 [2-O-methyl-11C]-(s)-N-((1-ethyl-2-pyrrolidinyl)-methyl)-5-bromo- 2,3-dimethoxybenzamide

    Extrastriatal dopamine D2 receptors in the brain

    [11C]Flumazenil Benzodiazepine receptors in the brain

    [11C]MeAIB α-[11C]methylamino-isobutyric acid System A amino acid transport [11C]Methionine Amino acid transport, tumours [11C]Metomidate O-[methyl-11C]-(R)-1-(1-phenethyl)-1H-imidazole-5-carboxylic

    acid methyl ester 11β-hydroxylase activity in adrenal cortical tissue

    [11C]MHED [11C]m-hydroxyephedrine Adrenergic innervation in the heart [11C]MP4A [methyl-11C]N-methylpiperidyl-4-acetate Acetylcholine esterase activity in the brain

    [11C]NMSP [11C]N-methyl-spiperone Dopamine D2 (striatum) and serotonin 5HT2 (extrastriatally) receptors in the brain

    [11C]NNC 756 [methyl-11C]-(S)-(+)-8-chloro-5-(2,3-dihydro-benzofuran-7-yl)-7- hydroxy-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine

    Dopamine D1 receptors in the brain

    [11C]Palmitate Fatty acid metabolism in the heart [11C]Raclopride Striatal dopamine D2 receptors in the brain

    [11C]SCH 23390 [methyl-11C]-(R)-(+)-8-chloro-5-2,3,4,5-tetra- hydro-3-methyl-5- phenyl-1H-3-benzazepin-7-ol

    Dopamine D1 receptors in the brain

    [11C]SCH 39166 [11C]Ecopipam Dopamine D1 receptors in the brain

    [11C]WAY 100635 [carbonyl-11C]N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N- (2-pyridyl)-cyclohexane- carboxamide

    Serotonin 5HT1A receptors in the brain

  • 14 May 2004 Turku PET Centre/ Olof Solin

    Turku PET Centre Today • 1400-1800 PET-studies /year • Scientific productivity (1993-2003)

    1993 1 Thesis 21 Articles 1994 1 Thesis 24 Articles 1995 2 Theses 45 Articles 1996 2 Theses 33 Articles 1997 41 Articles 1998 6 Theses 40 Articles 1999 6 Theses 56 Articles 2000 2 Theses 79 Articles 2001 9 Theses 79 Articles 2002 4 Theses 82 Articles 2003 8 Theses 80 Articles Total 41 Theses 586 Articles

    31 theses in progress

  • 14 May 2004 Turku PET Centre/ Olof Solin

    Radionuclide production Targetry and target chemistry

  • 14 May 2004 Turku PET Centre/ Olof Solin

    Cyclotron CC-18/9

  • 14 May 2004 Turku PET Centre/ Olof Solin

    Light emission during Nitrogen bombardment with protons

  • 14 May 2004 Turku PET Centre/ Olof Solin

    Gas target chamber for CC 18/9

  • 14 May 2004 Turku PET Centre/ Olof Solin

    Nuclear reactions for 18F

    • 20Ne(d,α)18F 20Ne(3He,αn)18Ne 18F

    • 16O(α,d)18F 16O(t,n)18F

    • 19F(p,d)18F 19F(p,2n)18Ne 18F

    • 18O(p,n)18F

  • 14 May 2004 Turku PET Centre/ Olof Solin

    Nuclide SAmax [Ci/µmol]

    11C 9200 13N 18800 15O 92000 18F 1700

    3H 0.029 14C 0.000062 32P 9.1

    -- Amount radioactivity/mass [Amount radioactivity/mass [Ci/Ci/µµmolmol]]

    -- SA theoretical maximumSA theoretical maximum

    SASAmaxmax= N= NAA * ln2 / T* ln2 / T1/21/2

    NA = Avogadros number

    Specific radioactivity, SA

  • 14 May 2004 Turku PET Centre/ Olof Solin

    •Substrate labeling (radiochemistry)

  • 14 May 2004 Turku PET Centre/ Olof Solin

    Synthesis of 18F labelled radiopharmaceuticals

    PRODUCTION OF 18F

    NUCLEOPHILIC 18F ELECTROPHILIC 18F

    NUCLEOPHILIC LABELLING

    ALKYLATION REAGENTS [

    18F]FLUOROMETHANE

    ALKYLATION SYNTHESIS OF [18F]F2

    ELECTROPHILIC LABELLING

  • 14 May 2004 Turku PET Centre/ Olof Solin

    Automated radiosynthesis

  • 14 May 2004 Turku PET Centre/ Olof Solin

    In vitroIn vitro human brain (100 human brain (100 µµm slices)m slices) A: Incubation with 40 pmol/L [18F]NK-1 tracer B: The same displaced with 1 µmol/L tracer

    A.

    B.

    NK 1 radioligand, in-vitro human brain study

  • 14 May 2004 Turku PET Centre/ Olof Solin

    BIOL PSYCHIATRY 2004;55:1007–1012 M. Bergstrom et alPredose (top) and postdose (bott