14 May 2004 Turku PET Centre/ Olof Solin
Turku PET CentreFinland
A Joint National Research Institute ofUniversity 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 andDisease
• Neurotransmission in Health and Disease
• Drug Discovery and Development
14 May 2004 Turku PET Centre/ Olof Solin
Turku PET Centre Functional Organisation
Metabolic ResearchPirjo Nuutila
Neurotransmission ResearchJarmo Hietala
Drug ResearchHarry Scheinin
National scientificboard
Management group Scientific project group
Quality ManagerPertti Lehikoinen
(GMP QA, TUCH PharmacyKirsti Torniainen)
CyclotronsStefan Johansson
AutomationTimo Saarinen
Radionuclide productionSven-Johan Heselius
F-18 ChemistryOlli Eskola
C-11 ChemistryKjell Någren
O-15 ChemistryHannu Sipilä
Laboratory functionNina Lauren
RadiochemistryJörgen Bergman
Preclinical imagingMerja Haaparanta
PET scanningHelena Luotolinna-Lybeck
Modelling and dosimetryVesa Oikonen
Information TechnologyPetri Numminen
ImagingMika Teräs
Diagnostic serviceHeikki Minn
DirectorJuhani Knuuti
Executive Board
Research projects
Radiochemistry ResearchOlof 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, boroncarrier 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 esterOpiate 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 ester11β-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 Articles1994 1 Thesis 24 Articles1995 2 Theses 45 Articles1996 2 Theses 33 Articles1997 41 Articles1998 6 Theses 40 Articles1999 6 Theses 56 Articles2000 2 Theses 79 Articles2001 9 Theses 79 Articles2002 4 Theses 82 Articles2003 8 Theses 80 ArticlesTotal 41 Theses 586 Articles
31 theses in progress
14 May 2004 Turku PET Centre/ Olof Solin
Radionuclide productionTargetry 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 Nitrogenbombardment 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 920013N 1880015O 9200018F 1700
3H 0.02914C 0.00006232P 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
NUCLEOPHILICLABELLING
ALKYLATIONREAGENTS [18F]FLUOROMETHANE
ALKYLATIONSYNTHESIS OF[18F]F2
ELECTROPHILICLABELLING
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 tracerB: 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 (bottom) PET scans at the level of the cerebellum (left) and striatum (right).
Estimated relationship between plasma concentration of aprepitant and occupancy of striatal NK1 receptors.
NK1 dose/occupancy study
14 May 2004 Turku PET Centre/ Olof Solin
Pharmacokinetics of positron emission tomography (PET) tracers in plasma
Digital autoradiography/ thin layer cromatographyDAR/TLC
Image of radioactivity distribution on TLC plate
Analysis of radioactivity distribution on TLC plateMolecular Imaging and Biology, 6 (2004) 27-33 Haaparanta et al.
14 May 2004 Turku PET Centre/ Olof Solin
4022453388468409423401441372240227200Total1596---------[18F]FDA
2912125--------[18F]FBPA
30--9183------[18F]FETNIM
1362913-314518-----[18F]SPA-RQ
79---13420213---[18F]F-
11221-17--19142219--[18F]FTHA
232-416182844524327--[18F]CFT
66116175961110807079626443[18F]FDOPA
2728366336362280203220284225132163157[18F]FDG
Total20032002200120001999199819971996199519941993
Number of PET studies
Production of Production of 1818FF--tracers during 1993tracers during 1993--20032003
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