1st Faculty of Medicine, Charles University in Prague Center for Advanced Preclinical Imaging (CAPI)
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1
2 Radioation
3 Resolution and Sensitivity
4 Nuclear Imaging PET + SPECT Radioactive Decay (EC,Ɣ), (β -,Ɣ), (I.T.,Ɣ) β + Projection imaging collimator needed one angular view Projection imaging coincidence imaging, no colimator needed complete set of angular views Single Photon Emission Computed Tomography (SPECT) Positron Emission Tomography (PET)
5 Functional Imaging Principles in Nuclear Imaging
6 Positron Emission Tomography PET
7 Positron Emission Tomography in vivo PET imaging Tomographic imaging modality Functional information Non-invasive High sensitivity pmol Short lived radioisotopes Large variety of labeled compounds Energy metabolism (FDG) Amino acid metabolism ( 18 F and 11 C labeled AA) Protein biosynthesis (DOTA conjugated puromycin analogues) Neurotransmitter Receptor imaging (neuro, onco, ) Hemodynamic parameters Gene expression Cell tracking (stem cells) 1-2 mm spacial resolution 6-10 % sensitivity temporal resolution < 0.5 sec QUANTIFIABLE
8 Positron Emission Tomography Positron Electron Annihilation Positron-emitting Rradionuclide e F 511 kev Photon Positron path-length depends on tissue density and positron energy 18 8O Positron-Electron Annihilation e + e kev Photon
9 Positron Emission Tomography Influence of Positron Energy on Resolution
10 Positron Emission Tomography Positron Emitting Radionuclides Isotope Halflife + fraction Max. Energy range(mm) production C mins MeV 0.4 mm cyclotron N mins MeV 0.7 mm cyclotron O secs MeV 1.1 mm cyclotron F mins MeV 0.3 mm cyclotron Cu mins MeV 2.7 mm generator Cu hours MeV 0.3 mm cyclotron Ga mins MeV 1.2 mm generator Br hours MeV 1.2 mm cyclotron Rb secs MeV 2.8 mm generator I days MeV 0.9 mm cyclotron
11 Positron Emission Tomography ALBIRA ɣ-ray Detector Principle PSPMT position sensitive photomultiplier tube Single continuous crystal Advanced Detector Electronics
12 Positron Emission Tomography Positron Electron Annihilation
13 Positron Emission Tomography Positron Electron Annihilation Current technology utilized packed crystals with dead zones Tighter packing yields more dead zones Susceptible to the parallax error (ignoring depth and order of interaction)
14 Positron Emission Tomography Operation of a PET-Scanner Scintilator Crystals Coincidence Unit Coincidences
15 Positron Emission Tomography ɣ-ray Detection in a PET system True Coincidences both ɣ-rays escape without scatter and interact in detctors Scatter coincidences one, or both ɣ-rays scatter in tissue Random coincidences two ɣ-rays from different origins strike the detectors at the same time (a.k.a. accidental coincidences)
16 Positron Emission Tomography Scatter Effects Buchholz et al., Eur J Nucl Med Mol Imaging (2003) 30:
17 Positron Emission Tomography Temporal resolution Consecutive 0.3-s frames show passage of tracer bolus through RV cavity, lungs, and LV chamber of mouse on coronal and transverse slices. Times are those after start of image acquisition / injection. For better anatomic orientation, PET scan is overlaid with coregistered CT scan. Michael C. Kreissl et al. J Nucl Med 2006;47:
18 Positron Emission Tomography PET Hardware Scintilators Light-Detectors Detectortype High stopping power High light output Fast scintillator Small crystal size High spatial resolution LSO, LYSO, YAP, etc. Photomultiplier Tubes (PMT) Single Channel Multi Channel Solid State Detectors Avalanche Photo Diodes (APD) Geiger-Mode APDs Silicon-PMTs Single Crystal Coupling Block Detector Detectors with DOI capabilities (Phoswitch) A full PET system comprises several detector rings summing up to several 1000 to individual crystals The performance of a PET system as well as physical limitations will be determined by the choice of hardware
19 Positron Emission Tomography Important Scanner Parameters Energy Resolution detection limit for measured energy of detected ɣ-rays Timing Resolution time variation (inaccuracy) of the system for detection of two single events originating from the same annihilation Spatial Resolution Sensitivity smallest object that can be visualized (partial volume effect) detection limit for radiotracer (isotope) or contrast media Temporal Resolution < 0.5 sec. per frame allows for fast kinetic acquisition (e.g. first pass of tracer through heart)
20 Single Photon Emission Computed Tomography SPECT
21 Single Photon Emission computed Tomography SPECT Tomographic imaging modality Functional information Non-invasive High sensitivity nmol (not as good as PET) Longer lived radioisotopes than PET Large variety of labeled compounds mm spatial resolution temporal resolution much slower than PET Quantification nearly impossible temporal resolution > 10 sec.
22 SPECT Gamma-Radiation 99m Tc 99 Tc + Ɣ Nucleus in an excited state decays to ground state 111 In 111 Cd + Ɣ Electron capture: Nucleus possesses too many protons but is unable to emit a positron and instead captures an electron 67 Cu 67 Zn + e - + Ɣ
23 SPECT Important SPECT Radionuclides
24 SPECT Anger Camera Anger camera (NaI-scintillator and photo multipliers) Hal Oscar Anger ( )
25 SPECT Scintillation Material
26 SPECT Parallel Hole Collimator
27 SPECT Parallel Hole Collimator
28 SPECT Pinhole Collimator Camera Obscura Magnification of the projected object
29 SPECT Pinhole vs. Parallel Hole Collimator Pinhole: Parallel hole: 177 LuCl 3 bone scan in a normal mouse
30 SPECT Multiple Pinhole Technology Higher sensitivity and better resolution
31 SPECT Multiple Pinhole Technology - Performance Choroid Plexus (folate receptor positive organ) 99mTc-Folate (tumor and kidney FR-positiv) female nude mice with human KB-cell tumors, 24 h p.i.
32 SPECT Principle of SPECT Flat panel head used for detection Acquisition time depending on: detector, collimator size of the imaging region amount of activity available. Multiple angle detection (minimum 2 detectors (180 ))
33 SPECT Dual Isotope Imaging 99m Tc-MDP (red-blue) bone scintigraphy 99m Tc (140.5 kev) 123 I (green-yellow) thyroid imaging 123 I (159.0 kev)
34 Functional Imaging Tracer Principle A radioactive tracer is a chemical compound in which one or more atoms have been replaced by a radioisotope. It is applied in minimal amounts, therefore, it has no pharmacologic effect in vivo. It can also be used to explore the mechanism of bio- /chemical reactions by tracing the path that the radioisotope follows from reactant to product George de Hevesy ( ); Nobel Prize for Chemistry in 1943 E.g. 370 MBq of 11 C-tracer necessary for a brain scan with 11 C-Raclopride (D2-receptor ligand) corresponds to 100 picogram total mass injected.
35 Radiopharmacy Radionuclide Production Cyclotron C-11 N-13 F-18 Cu-64 Cu-67 In Reactor (neutron bombardment) I-131 Sm-153 Ho-166 Lu-177 W-188 Radionuclide generators Sc-44 Ga-68 Tc-99m Re-188
36 Radiopharmacy Do we need so many radionuclides?
37 Radiopharmacy Radionuclides for Diagnosis Direct labeling with non-metal radionuclides Indirect labeling strategies via bifunctional chelators 60 % of suitable radionuclides are metals!
38 Radiopharmacy Radiolabeling Critical Issues of Functionalization organic inorganic Labeling yields Synthetic steps Avoid cross reactivity with other functional groups Avoid mixtures of products and formation of isomers Optimal pharmacokinetic Retention of biological activity and integrity
39 Radiopharmacy Radiotracer Production
40 THANK YOU FOR YOUR ATTENTION
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