I have financial relationships to disclose Research support from: Siemens Medical Solutions

I have financial relationships to disclose Research support from: Siemens Medical Solutions

Nuklearmedizinische Klinik im Klinikum rechts der Isar der Technischen Universität München PET Imaging Tracers and Protocols for Routine Clinical Use Markus Schwaiger, Stephan Nekolla Technische Universität München Germany 2012 Annual ESC Congress, August 25. 29. 2012 München, Germany

PET Cardiology Applications and Protocols Clinical Measurements of Perfusion (Flow Reserve) Assessment of Tissue Viability Integrated Phenotyping of CAD Research Endothelial Function Plaque Imaging Molecular Imaging (HF, Innervation, Inflammation) Therapy Monitoring (Cell Therapy, HF)

Multimodal Cardiac Imaging Anatomy, Function and Molecular Tissue Characterisation Multimodal Imaging SPECT/CT, PET/CT, PET/MRI SPECT/CT PET/CT PET/MRI

PET/MRI (mmr Biograph)

mmr Biograph Simultaneous MRI and PET Acquisition Function and Viability

MR/CT/PET Examination 18 F-FDG PET/CT acquired with a Biograph16 PET/CT MRI acquired with 1.5 T (TR: 0.2 ms, TE: 0.7 ms) Attenuation Correction performed using a segmentation-based method. No AC CT AC MR AC Martinez; Nekolla et al

PET Tracer Molecular Imaging Probes Wester HJ, Clin Cancer Res. 2007 HED,MIBG

SPECT PET Myocardial Perfusion Imaging Perfusion Tracer Tracer HWZ g - kev EF(%) Tl-201 72 h 80, 165 80 Tc-99m MIBI 6 h 140 65 Tc-99m Tetrofosmin 6 h 140 60 O-15 Water 2 min 511 100 N-13 Ammonia 10min 511 90 Rubidium-82 76 sec 511 65 F-18 Fluripidaz 119min 511 95

F-18 Flow tracer F-18 Fluripidaz Imaging Contrast myo/blood myo/liver myo/lung NH3 Stress 1.8±0.1 0.7±0.0 2.0±0.3 NH3 Rest 2.5±0.1 1.2±0.1 2.5±0.5 F-18 Fluripidaz S F-18 Fluripidaz R 5.8±0.5 2.0±0.1 6.4±1.1 4.1±0.7 1.8±0.1 4.9±1.5 Nekolla et al, Circulation

RA LA LV All slides TU München. No use without permission. Time Fluridipaz Perfusion Imaging Ischemia Model (120 sec occlusion) RV RA LV LA

Rubidium-82 Imaging Protocol 920MBq 82 Rb (rest) 140 ug/kg/min Adenosine over 5 min. Injection of 934MBq 82 Rb (stress) after 2.5 min Dynamic acquisitions Listmode Transmission Dynamic 10 min 6 min Dynamic 10 min i.v. 30 sec bolus 82 Rb ~1000 MBq Adenosine i.v. 30 sec bolus 82 Rb ~1000 MBq

82 Rb: Time activity curves 600000 500000 Blood Rest Mean Tissue Rest Blood S1 Mean Tissue S1 400000 Activity in Bq/ml 300000 200000 MBF = 2.8 ml/min/g 100000 MBF = 0.8 ml/min/g 0 0 50 100 150 200 250 300 350 400 450 Time / seconds

Quantitative Flow and Flow Reserve MBF Rest MBF Dipyridamole Flow Reserve MBF Rest Stress CFR LAD 0.72 2.31 3.3 LCX 0.86 2.75 4.3 Retention Model w. Extraction Correction RCA 0.65 2.68 3.2 Global 0.72 2.42 3.4 ml/min/g Bengel

Quantification of Flow Multimodal Imaging with PET/CT (O-15 water) Kajander, et al Circulation/2010

First simultaneous measurement of myocardial perfusion on whole-body PET/MR Hybrid MPI Protocol MRI Slice planning T1 map AC SR GRE Cine T1 map AC SR GRE LGE AC Adenosine Gd: 4mL/s 0.05mmol/kg Gd: 4mL/s 0.05mmol/kg Gd: 2mL/s 0.1 mmol/kg 13 NH 3 : 0.67mL/s 214±31 MBq in 20 ml 13 NH 3 : 0.67mL/s 214±31 MBq in 20 ml 0 min 60 min 15-min Listmode 15-min Listmode PET Zhang, Nekolla, Schwaiger

First simultaneous measurement of myocardial perfusion on whole-body PET/MR Acquisition of first-pass DCE ( AIF and myocardium seperated) 5.94 x 5.94 x 10 mm 3 TI/TE=5/0.63ms 1.98 x 1.98 x 8mm 3 TI /TE = 100/1.05ms AIF slice Apical Slice Mid-Ventrical Slice Basal Slice 12.5ms 150ms 325ms 500ms Nonselective 90 o pulse train Nonselective 90 o pulse train Nonselective 90 o pulse train Nonselective 90 o pulse train 1. Gatehouse PD et al J Magn Reson Imaging. 2004; 20(1):39-45. 2. Xue H et al Med Image Comput Comput Assist Interv. 2009;12:741-9.

MR Perfusion [ml/min/g] MR Perfusion [ml/min/g] First simultaneous measurement of myocardial perfusion on whole-body PET/MR PET/MRI MPI Midventricular Slice 3 MidLV (slice average) Identity Line 3,5 MidLV (6 segments) 2,5 3 2 2,5 1,5 1 0,5 y = 0.49x + 0.48 R² = 0.98 2 1,5 1 0,5 y = 0.44x + 0.55 R² = 0.72 0 0 1 2 3 PET Perfusion [ml/min/g] 0 0 0,5 1 1,5 2 2,5 3 3,5 PET Perfusion [ml/min/g] Zhang, Nekolla, Schwaiger

ml/min/g Flow Reserve First simultaneous measurement of myocardial perfusion on whole-body PET/MR Global Myocardial Perfusion ( 3 slices) 3 2,5 PET MR 3,5 3 PET MR 2 1,5 1 2,5 2 1,5 1 0,5 0,5 0 REST STRESS 0 Zhang, Nekolla, Schwaiger

Imaging Parameters of Viability Viable Non-viable Residual Perfusion / Reserve (SPECT/PET) Contractile Reserve (ECHO/MRI/SPECT/PET) Oxidative Metabolism (PET,MRS) Glucose Utilization (PET, MRS) Membrane Integrity (SPECT) GD-DTPA Enhancement (MRI/CT) Apoptosis / Myosin Antibody (SPECT)

Injection 18 F-FDG (240-370 MBq) PET/MR-Protocol (viability/clamp) Injection 13 N-ammonia (350 MBq) Gd (0.1 x BW) 13 N PET / MR PERFUSION (Rest) Injection Gd (0,3 x BW) 13 N PET / MR LATE ENHANCEMENT Insulin- Glucose-Clamp PET VIABILITY MR - SCOUT (axial, coronal, sagittal) - CINE (2Ch, 4Ch, Shax) 18 F-FDG PET Native MR 45 15 15 10

PET/MR: 6 days post MI LCE MRI Corr. FDG PET Glucose/Insulin Clamp

PET/MR: 6 days post MI

Tissue Viability/ Inflammation Fasted FDG Imaging 4 days after Myocardial Infarction Ripschler et al

Metabolic Memory FDG 5 Days after Acute Ischemic Event A B C D Takotsubo Ibrahim, Nekolla,Ripschler

PET/CT/MR Multimodal Cardiac Imaging Applications in Nuclear Cardiology Clinical Multimodal phenotyping of CAD Assessment of tissue viability / necrosis Integrated plaque imaging (?) Research Crossvalidation of imaging methods (i.e. perfusion) Molecular imaging (innervation,receptors,inflammation) Monitoring therapy i.e.cell therapy /cell migration

Acknowledgements Ambros Beer Alexander Drzezga Michael Souvatzoglou Iina Laitinen Isabel Dregely Sebastian Fürst Stephan Nekolla Sybille Ziegler Axel Martinez- Möller Sandra v Marwick Hans Jürgen Wester Sebastian Fürst Petra Watzlowik Shelley HuaLei Zhang, Christoph Rischpler, Carmel Hayes, Florian Gaertner, Gitti Dzewas Coletta Kruschke Sylvia Schachoff