Molecular Imaging of Coronary Plaques

Transcription

1 Molecular Imaging of Coronary Plaques Daniel S. Berman, MD Director, Cardiac Imaging Cedars-Sinai Heart Institute CSMC Professor of Medicine David Geffen School of Medicine at UCLA Zahi A. Fayad, PhD, FAHA, FACC Professor of Radiology Rdil and Medicine Mdii (Cardiology) Director, Translational and Molecular Imaging Institute Mount Sinai School of Medicine, New York, NY 1

2 David Newby, MD Mark kdweck, MD University of Edinburgh Understanding CAD is Changing Fibroatheroma: Stable Plaque Narula & Willerson, JACC (ed) TCFA with Cap Rupture Narula & Virmani,

3 Anatomical to Molecular Imaging Tissue level Anatomical level Cellular and molecular Level Imaging Probes Sensitivity PET MRI CT Radioactive Small Molecules Paramagnetic Superparamagnetic Radiodense Payload required 3

4 Imaging Probes Sensitivity PET MRI CT Radioactive Small Molecules Paramagnetic Superparamagnetic Radiodense Payload required Orders of Magnitude in Drug (Contrast Agent) Dosing: Exploiting the Exploratory IND (eind) Mechanism Modality CT Typical Intravenous Human Dose (g) 75 cc of 930 mm solution = 56 g MRI 15 cc of 500 mm solution = 7g Regular Strength Tylenol = 600 mg Optical (NIR) 5 cc of a 1 mm solution = 5 mg FDA definition of micro-dosing = 100 µg SPECT 20 mci (10,000 Ci/mmol) = 2 µg eind PET 20 mci (10,000 Ci/mmol) = 2 µg Eligible 4

5 FDG Uptake in Carotid Artery Disease FDG-PET CTa Fused 10 FDG accumulation Rate/sec 5 P<0.01 SymptomsNo symptomatic asymptomatic symptoms Weissberg P et al., Circulation 2004 Simvastatin Attenuates Plaque Inflammation Tahara et al JACC

6 Tawakol et al JACC 2006 Measuring atherosclerosis FDG PET/CT Identifies cells with increased metabolic activity Measures plaque glycolysis (inflammation) Usedto assess changes inplaque inflammation Statins, anti inflammatory drugs, TZDs Predictor of future risk of atherothrombosis 18F FDG PET/CT imaging 5 PET/C CT CT 1 Rudd et al. Circulation. 2002;105; ; 2 Rudd et al. J Am Coll Cardiol. 2010;55: ; 3 Tahara et al. J Am Coll Cardiol. 2006;48: ; 4 Lee et al. J Nucl Med. 2008;49: ; 5 Fayad et al. The Lancet 2011;378:

7 FDG Visualization of Inflamed Coronary Plaque FDG Visualization of Inflamed Coronary Plaque 7

8 27 PCI patients studied with FDG PET/CT 1-6 days p PDI: 20 STEMI; 7 stable CAD Increased uptake in: 12/20 STEMI; 1/7 Stable Cheng, et al JNM in press 2012 Figure 3 FDG Uptake at Stent Site in Acute STEMI CORONAL AXIAL SAGITTAL LAD STEMI RCA STEMI LCX STEMI Cheng, et al JNM in press

9 Absence of FDG Uptake at Stent Site in Stable CAD CORONAL AXIAL RCA stent for stable CAD SAGITTAL LAD stent for stable CAD Cheng, et al JNM in press 2012 Sinusas lecture: ASNC

10 Direct Imaging of Myocardial Ischemia (FDG) He et al, Narula, Jain. Circulation Fluoro-Deoxy Glucose The ring of fire Aortic Ring Inflammation Dweck et al. Circulation 2012;125:in press 10

11 Sodium 18 Fluoride Aortic Stenosis Dweck et al. Circulation 2012;125: Fluoro-Deoxy Glucose The ring of fire Dweck et al. Circulation 2012;125:

12 Calcification more important than Inflammation Dweck et al. Circulation 2012;125:76-86 Dweck et al JACC

13 F-18 NaF Uptake in Coronary Plaque Dweck M Newby D ACC year FRS for Controls and Patients with CAC who did and did not have 18F-NaF uptake Dweck et al JACC

14 Tc-99m Annexin V: Probe for Vulnerable Plaque TNF or Fas Ligand Annexin V Detection of the apoptotic cell binding followed by 2D-crystallization TNFR or death domains mediated signaling scramblase translocase CD ? floppase activation of the executioner of apoptosis Courtesy Chris Reutlingsperger, Maastricht University ANT L Annexin-V Imaging For Apoptosis A Old TIA B Recent TIA Transverse Coronal C D Keitselaar, Hofstra, Narula; NEJM 2004 Annexin IHC in Endarterectomy 14

15 RGD tracer uptake is increased in atherosclerotic plaque Oil Red O 18 F RGD uptake αvβ3 Autoflour Tamarappoo, et al 2010 Direct Imaging of Myocardial Ischemia (FDG) He et al, Narula, Jain. Circulation

16 Molecular Imaging to Detect Vulnerable Plaque Clinial Applications Emerging in 2020 Langer et al. JACC 2008; 52:1-12. Molecular Imaging Across CAD Spectrum Conventional Imaging Coronary Calcium/ Plaque Stenosis/ Perfusion Function Geometry Coronary Atherosclerosis Myocardial Ischemia/ Infarction Heart Failure Molecular Imaging Disease Activity Plaque Vulnerability Remodeling Guiding Specific therapy 16

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