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Atherosclerotic plaque:  Radionuclide Imaging Human Adams
Introduction Genomics Proteomics (complex) molecular pathways Atherosclerotic plaque Molecular ‘events’ Stenosis
 
Introduction – Role of molecular imaging Genomics Proteomics (complex) molecular pathways Molecular ‘events’ Stenosis (uns...
The “Vulnerable plaque” <ul><li>Anatomic plaque imaging: </li></ul><ul><ul><li>64 -320 MDCT </li></ul></ul><ul><ul><li>Dua...
Introduction – non-invasive molecular imaging Molecular Imaging? Selection of target Synthesizable probe Labelling for Ima...
Introduction – Radionuclide imaging <ul><li>Detection molecule in p icomolar - nanomolar range  </li></ul><ul><li>(>10 7  ...
Radionuclide imaging of the plaque
 
Radionuclide imaging of the plaque <ul><li>Metabolic activity </li></ul><ul><li>Plaques have higher metabolic activity </l...
Radionuclide imaging of the plaque:  18 F-FDG PET -CT JNM 16-3-’09
Radionuclide imaging of the plaque
Radionuclide imaging of the plaque:  18 F-FCH PET -CT JNM 16-3-’09 Matter et al
Radionuclide imaging of the plaque <ul><li>Chemotaxis </li></ul><ul><li>Visualise expression of chemokines </li></ul><ul><...
Radionuclide imaging of the plaque:  125 I-MCP-1
Radionuclide imaging of the plaque <ul><li>Angiogenesis/ α v β 3  integrin </li></ul><ul><li>Evidence suggests that the ex...
Radionuclide imaging of the plaque <ul><li>Lipoproteins </li></ul><ul><li>Particularly low-density lipoproteins (LDLs), co...
Radionuclide imaging of the plaque:  124 I-CD68-Fc <ul><li>Proteolysis </li></ul>
Radionuclide imaging of the plaque:  Annexin V <ul><li>Apoptosis </li></ul>
Radionuclide imaging of the plaque:  Annexin V <ul><li>Apoptosis </li></ul>
Conclusions: Radionuclide imaging of the plaque <ul><li>Identifying high-risk plaques could transform clinical management ...
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Atherosclerotic plaque: Radionuclide Imaging

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Atherosclerotic plaque: Radionuclide Imaging

  1. 1. Atherosclerotic plaque: Radionuclide Imaging Human Adams
  2. 2. Introduction Genomics Proteomics (complex) molecular pathways Atherosclerotic plaque Molecular ‘events’ Stenosis
  3. 4. Introduction – Role of molecular imaging Genomics Proteomics (complex) molecular pathways Molecular ‘events’ Stenosis (unstable) plaque Reperfusion <ul><li>Severity </li></ul><ul><li>Localisation </li></ul><ul><li>Lab tests </li></ul><ul><li>Imaging </li></ul>Angiography Therapy
  4. 5. The “Vulnerable plaque” <ul><li>Anatomic plaque imaging: </li></ul><ul><ul><li>64 -320 MDCT </li></ul></ul><ul><ul><li>Dual source CT </li></ul></ul><ul><ul><li>Electron Beam CT </li></ul></ul><ul><ul><li>MRI </li></ul></ul><ul><ul><li>IVUS </li></ul></ul><ul><li>Molecular imaging </li></ul><ul><li>Hybrid imaging </li></ul>
  5. 6. Introduction – non-invasive molecular imaging Molecular Imaging? Selection of target Synthesizable probe Labelling for Imaging modality <ul><li>Specific receptors </li></ul><ul><li>Specific pathway </li></ul><ul><li>Specific metabolic activity </li></ul><ul><li>Nuclear </li></ul><ul><li>MRI </li></ul><ul><li>Optical fluorescence </li></ul><ul><li>Bioluminescence </li></ul>T/S resolution Signal sensitivity Practical limitations
  6. 7. Introduction – Radionuclide imaging <ul><li>Detection molecule in p icomolar - nanomolar range </li></ul><ul><li>(>10 7 more than other modalities) </li></ul><ul><li>Spatial resolution: PET 4-5 mm (SPECT 10-15mm) </li></ul><ul><li>Radiation dose: </li></ul><ul><li>CT: abdomen 10-12 mSv </li></ul><ul><li>CT: cardiac 12-22 mSv </li></ul><ul><li>Low dose CT: 5-8 mSv </li></ul><ul><li>Whole body PET: 2-4 mSv </li></ul><ul><li>Chest X-ray: 0,1 mSv </li></ul>Positron emission (Beta+) Cosmic background radiation / year: 1,5-2 mSv Flight crew: 2-5 mSv Radiolabeling
  7. 8. Radionuclide imaging of the plaque
  8. 10. Radionuclide imaging of the plaque <ul><li>Metabolic activity </li></ul><ul><li>Plaques have higher metabolic activity </li></ul><ul><li>Tracers: 18 F-Fluorodeoxyglucose (FDG) </li></ul><ul><ul><ul><ul><li> 18 F-Fluorocholine (FCH) </li></ul></ul></ul></ul><ul><li>FDG: competes with glucose: uptake in metabolic active cells (macrophages) </li></ul><ul><li>FCH: choline derivative, phophorylated by choline kinase to phosphatidylcholine, incorporated in highly proliferative cells (tumor cells, activated macrophages) </li></ul><ul><li>Preliminary studies: sensitivity FCH > FDG </li></ul>
  9. 11. Radionuclide imaging of the plaque: 18 F-FDG PET -CT JNM 16-3-’09
  10. 12. Radionuclide imaging of the plaque
  11. 13. Radionuclide imaging of the plaque: 18 F-FCH PET -CT JNM 16-3-’09 Matter et al
  12. 14. Radionuclide imaging of the plaque <ul><li>Chemotaxis </li></ul><ul><li>Visualise expression of chemokines </li></ul><ul><li>Monocyte chemoattractant protein (MCP)-1 </li></ul><ul><li>Strongest chemotactic agent to atherosclerotic plaque </li></ul><ul><li>Does not express in healthy tissue, only by various stimuli (TNF/ cytokines ) </li></ul><ul><li>Tracers: 125 I-MCP-1 </li></ul><ul><ul><ul><li>(VCAM-1) </li></ul></ul></ul><ul><ul><ul><li>(antigen-4) </li></ul></ul></ul>
  13. 15. Radionuclide imaging of the plaque: 125 I-MCP-1
  14. 16. Radionuclide imaging of the plaque <ul><li>Angiogenesis/ α v β 3 integrin </li></ul><ul><li>Evidence suggests that the extent of neovascularization is closely linked to the inflammatory reaction and infiltration of macrophages/foam cells within atherosclerotic plaques </li></ul><ul><li>α v β 3 integrin is highly expressed in angiogenic or activated endothelial cells but not, or to a much lower extent, in quiescent endothelial cells </li></ul><ul><li>Tracers: Radioactive-labeled α v β 3 integrin peptides </li></ul><ul><li>18 F-Galacto-RGD α v β 3 integrin (expression) </li></ul>
  15. 17. Radionuclide imaging of the plaque <ul><li>Lipoproteins </li></ul><ul><li>Particularly low-density lipoproteins (LDLs), contribute to early lesion formation </li></ul><ul><li>Oxidized lipoproteins initiate and sustain the inflammation process and are essential for foam cell generation </li></ul><ul><li>S cavenger receptors (e.g., CD68, SR-A, CLA-1/SR-BI, CD36, LOX-1, and SR-PSOX) are mediating the uptake of lipoproteins, into macrophages </li></ul><ul><li>Tracers: 124 I-CD68-F </li></ul>
  16. 18. Radionuclide imaging of the plaque: 124 I-CD68-Fc <ul><li>Proteolysis </li></ul>
  17. 19. Radionuclide imaging of the plaque: Annexin V <ul><li>Apoptosis </li></ul>
  18. 20. Radionuclide imaging of the plaque: Annexin V <ul><li>Apoptosis </li></ul>
  19. 21. Conclusions: Radionuclide imaging of the plaque <ul><li>Identifying high-risk plaques could transform clinical management </li></ul><ul><li>Essential to acquire information beyond the resulting degree of stenosis </li></ul><ul><li>Molecular imaging may identify risk lesions not found by routine evaluation </li></ul><ul><li>Atherosclerosis-targeted imaging agents are on the clinical horizon </li></ul>Clinical perspective Langer et al. JACC Vol. 52, No. 1, 2008 radionuclide Imaging in Atherosclerosis

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