Nuclear Biomedical Imaging, Preclinical And Clinical Studies With Focus On Oncology
Summary
Samenvatting nucleaire biomedische beeldvorming (Ma Moleculaire)
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Course
Nuclear Biomedical Imaging, Preclinical And Clinical Studies With Focus On Oncology
Institution
Universiteit Antwerpen (UA)
Dit is een samenvatting van de slides met notities van het vak Nucleaire biomedische beeldvorming, preklinische en klinische studies met focus op oncologie.
nucleaire biomedische beeldvorming preklinische en klinische studies met focus op oncologie
moleculaire mechanismen van ziekten
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Universiteit Antwerpen (UA)
Biomedische Wetenschappen
Nuclear Biomedical Imaging, Preclinical And Clinical Studies With Focus On Oncology
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NUCLEAIRE BIOMEDISCHE
BEELDVORMING
INHOUDSOPGAVE
1.1 Wat is nucleaire biomedische beeldvorming? ........................................................................................... 5
1.2 SPECT (single photon emission computerized tomography) ..................................................................... 5
1.2.1 Humaan SPECT....................................................................................................................................... 5
1.2.1.1 Nucleaire aspect ........................................................................................................................... 5
1.2.2 Small animal SPECT ................................................................................................................................ 6
1.3 PET (positron emissie tomografie) ............................................................................................................. 6
1.3.1 Humaan PET........................................................................................................................................... 6
1.3.2 Small animal PET .................................................................................................................................... 7
2.1 Radiofarmaceutica ..................................................................................................................................... 8
2.2 Ontwikkeling van radiofarmaceutica ......................................................................................................... 8
2.2.1 Bepaling van het target ......................................................................................................................... 8
2.2.2 Vehicle, vector or targeting molecule ................................................................................................... 9
2.2.3 Keuze van radio-isotoop ........................................................................................................................ 9
2.2.3.1 Radiofarmaceutica voor diagnose ................................................................................................ 9
2.2.3.2 Radiofarmaceutica voor therapie ............................................................................................... 10
2.2.3.3 Beschikbaarheid van het radio-isotoop ...................................................................................... 10
2.2.4 Radiolabeling en optimalisatie van radiolabeling ................................................................................ 11
2.2.5 Zuivering van precursor en ongebonden radiolabel ............................................................................ 12
2.2.6 Steriele formulering en quality control van RF .................................................................................... 12
2.2.7 In vitro evaluatie .................................................................................................................................. 13
2.2.8 In vivo evaluatie ................................................................................................................................... 13
2.3 Vereisten voor radiofarmaca ................................................................................................................... 13
2.4 RF voor beeldvorming in de oncologie .................................................................................................... 14
2.4.1 Glucose metabolisme: 18F-fluorodeoxyglucose ................................................................................... 14
2.4.2 Hypoxie beeldvorming ......................................................................................................................... 14
2.4.3 Proliferatie beeldvorming: [18F]FLT .................................................................................................... 15
2.5 RF voor beeldvorming in de neurologie ................................................................................................... 15
2.5.1 Beeldvorming van het dopaminesysteem ........................................................................................... 15
2.5.2 Beeldvorming van het serotoninesysteem .......................................................................................... 16
2.5.3 Beeldvorming van de GABA-receptor .................................................................................................. 16
2.5.4 Beeldvorming in de ziekte van Alzheimer ........................................................................................... 16
, 2.5.5 Brain perfusie ...................................................................................................................................... 17
3.1 Introductie ............................................................................................................................................... 18
3.2 Basisprincipes........................................................................................................................................... 18
3.2.1 PET vs SPECT tracers ............................................................................................................................ 18
3.2.2 SPECT ................................................................................................................................................... 19
3.2.3 PET ....................................................................................................................................................... 19
3.3 Diagnose en staging ................................................................................................................................. 20
3.3.1 Diagnose .............................................................................................................................................. 20
3.3.2 Kanker staging (TNM staging) .............................................................................................................. 20
3.4 Voorbij FDG in lage of non-FDG gevoelige tumoren ................................................................................ 21
3.4.1 Somatostatine receptor beeldvorming ............................................................................................... 21
3.4.2 PSMA-PET ............................................................................................................................................ 22
3.4.3 FET en FAPi-PET ................................................................................................................................... 22
3.5 Detectie van recidief ................................................................................................................................ 22
3.6 Therapie respons evaluatie ...................................................................................................................... 23
3.7 Personalized Medicine ............................................................................................................................. 24
3.8 Radionucleïde therapie: theranostics ...................................................................................................... 25
4.1 Introduction ............................................................................................................................................. 26
4.1.1 Evidence based medicine .................................................................................................................... 26
4.1.2 Nadelen in vitro modellen ................................................................................................................... 26
4.1.3 In vivo modellen .................................................................................................................................. 27
4.2 Overview: in vivo cancer models ............................................................................................................. 27
4.2.1 Syngeneïsche modellen ....................................................................................................................... 27
4.2.2 Xenogeneïsche modellen..................................................................................................................... 28
4.2.3 Immunodeficiënte muismodellen ....................................................................................................... 29
4.2.4 Locatie van inoculatie/implantatie ...................................................................................................... 29
4.2.4.1 Subcutane kankermodellen ........................................................................................................ 29
4.2.4.2 Orthotope kankermodellen ........................................................................................................ 30
4.2.4.3 Andere in vivo kankermodellen .................................................................................................. 30
4.2.5 Rat models in cancer research ............................................................................................................. 30
4.2.5.1 De athymische naakte rat ........................................................................................................... 30
4.2.5.2 Voordelen van rat modellen ....................................................................................................... 31
4.3 Molecular Imaging Modalities ................................................................................................................. 32
4.3.1 Bioluminescene (BLI) ........................................................................................................................... 33
4.3.2 Fluorescence molecular imaging (FMT) ............................................................................................... 34
4.3.3 Positron emmision tomography (PET) ................................................................................................. 34
4.4 Preclinical cancer models for PET imaging ............................................................................................... 35
, 4.4.1 Tumor metabolisme (18F-FDG)............................................................................................................. 35
4.4.1.1 Vasten – opwarmen .................................................................................................................... 36
4.4.1.2 FDG injectie ................................................................................................................................. 36
4.4.1.3 Anesthesie................................................................................................................................... 36
4.4.1.4 Bloed glucose levels .................................................................................................................... 37
4.4.2 Tumor proliferatie (18F-FLT) ................................................................................................................. 37
4.4.3 Tumor apoptose (99mTc-Annexin A5, 18F-CP18,…) ................................................................................ 38
4.4.4 Tumor hypoxia (18F-FMISO, 18F-HX4) ................................................................................................... 39
5.1 Introductie ............................................................................................................................................... 42
5.2 SPECT instrumentatie ............................................................................................................................... 43
5.2.1 Collimators ........................................................................................................................................... 43
5.2.1.1 Parallel beam collimatie.............................................................................................................. 44
5.2.1.2 Converging beam collimator ....................................................................................................... 45
5.2.1.3 Pinhole imaging........................................................................................................................... 45
5.2.2 Detectors ............................................................................................................................................. 46
5.2.2.1 Scintillatie detectie ..................................................................................................................... 46
5.2.2.2 Anger logica ................................................................................................................................ 47
5.2.2.3 Photon multiplier tube (PMT) ..................................................................................................... 48
5.3 Image degradation ................................................................................................................................... 48
5.3.1 Attenuatie en verstrooiing................................................................................................................... 48
6.1 PET techniek – overview .......................................................................................................................... 50
6.2 Time of flight (TOF) PET ........................................................................................................................... 50
6.3 PET in nucleaire beeldvorming ................................................................................................................ 51
6.4 Positron Emission Tomography principe ................................................................................................. 51
6.5 PET in de praktijk ..................................................................................................................................... 51
6.5.1 PET gebruik .......................................................................................................................................... 51
6.5.2 Isotoop productie ................................................................................................................................ 52
6.6 Technische aspecten van PET scanners ................................................................................................... 52
7.1 Statische PET beeldvorming ..................................................................................................................... 55
7.2 SUV kwantificatie ..................................................................................................................................... 56
7.2.1 Activiteitsconcentratie......................................................................................................................... 56
7.2.2 SUV kwantificatie ................................................................................................................................. 56
7.2.3 Opmerkingen bij de SUV-berekening .................................................................................................. 57
7.2.4 Statische kwantificatie ......................................................................................................................... 57
7.2.5 SUV tumor ........................................................................................................................................... 57
7.2.6 Statische beeldvorming ....................................................................................................................... 58
7.3 Dynamische PET beeldvorming ................................................................................................................ 59
, 7.4 Farmacokinetische modellering ............................................................................................................... 60
7.4.1 Wat is farmacokinetische modellering ................................................................................................ 60
7.4.2 Compartimentenmodel ....................................................................................................................... 60
7.4.3 Input functie ........................................................................................................................................ 62
7.4.4 One tissue compartmental model (1TCM) .......................................................................................... 62
7.4.5 Two tissue compartmental model ....................................................................................................... 64
7.4.6 Micro & macro -parameters ................................................................................................................ 65
7.5 Zelftest ..................................................................................................................................................... 65
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