핵의학

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1 PET/MR and PET/CT for Coronary Artery Disease: Prime Time or Not? Jin Chul Paeng, MD Department of Nuclear medicine Seoul National University Hospital

2 Contents PET Imaging in Coronary Artery Disease FDG PET Myocardial Perfusion PET Recent Advances in PET for Coronary Artery Disease Instrument (hybrid imaging of PET/MR and PET/CT) Image analysis Radiopharmaceuticals Clinical needs The Question: Is It Prime Time or Not?

3 PET Imaging in CAD FDG PET Perfusion PET

본인일부부담금산정특례에관한기준 ( 보건복지부고시 ) [ 별표 3( 중증질환 )] 의구분 1~3과 [ 별표 4( 희귀난치성질환 )] 으로분류된질환범주 ( 암,

4 FDG PET for Viability Assessment Energy Metabolism Preserved glucose (anaerobic) metabolism Perfusion-metabolism mismatch Current Reimbursement by K-NHIS (Since 2006) 1. 본인일부부담금산정특례에관한기준 ( 보건복지부고시 ) [ 별표 3( 중증질환 )] 의구분 1~3과 [ 별표 4( 희귀난치성질환 )] 으로분류된질환범주 ( 암, 뇌혈관, 심장, 희귀난치성질환 ) 의경우에는아래의범위내에서요양급여를인정함. NH 3 나. 허혈성심질환에서심근의생존능평가 : 치료전, 치료 후각각 1 회로인정함 FDG

5 Perfusion PET (in comparison with SPECT) Why PET? Better image quality CT attenuation correction Localization Sensitive for mild change Low radiation dose: 1.5 to 5 msv Patients convenience Absolute flow measurement with ease Tracers: 15 O-water, 13 N-ammonia, 82 Rb, 18 F-flurpiridaz Higher extraction fraction of PET tracers Easy dynamic scan for kinetic analysis

6 Perfusion PET Quality & Accuracy Rb-82 PET Heller et al. JNC 2009 (Modified from Yoshinaga et al. Circulation 2006) Bateman et al. JNC 2006

8 Flow Quantification

9 M/61. Underlying DM, CRF without symptom Screening CT CAG: plad 50% CAG: LM and LAD: diffuse, FFR 0.61 dlcx: 40%, FFR 0.78 / drca 60% FFR 0.78 Medical F/U and NH 3 PET after 1.5 years

10 Flow Quantification Referred for CABG

11 Needs for Functional Study: FAME I FAME (Fractional Flow Reserve vs. Angiography for Multivessel Evaluation) FFR-guidance deferred 37% of PCI with better outcomes. Pijls et al. J Am Coll Cardiol 2010;56:177 > >

12 FAME II Angiographically Proven Stenosis In 25%, FFR was not significantly low. Regarding FFR <0.80, significantly different outcome De Bruyne et al. New Engl J Med 2012;367:991

13 FFR vs. CFR CFR (Coronary Flow Reserve) Absolute CFR: ratio of maximum stress flow to rest flow Relative CFR: ratio of maximum stress flow in the diseased artery to maximum stress flow in the absence of disease in either the same or adjacent arterial distribution Gould et al. J Am Coll Cardiol 2013;62:1639 CFR on Perfusion Imaging vs. FFR FFR: Q s /Q n (= relative CFR) De Bruyne et al. Circulation 1994;89:1013 Marques et al. J Nucl Med 2007;48:1987

14 Functional Imaging Studies Modality Methods Pro Con CT Perfusion Dynamic enhancement Semi-kinetic analysis Easy Radiation (dynamic) Need for validation MR Perfusion Dynamic enhancement Semi-kinetic analysis No radiation Need for validation Cost CT FFR Hydraulic assumption with 3D CTA Accessibility Radiation Need for validation SPECT Difference in uptake Kinetic analysis Accessibility Validation Radiation Image quality (vs. PET) PET Difference in uptake Kinetic analysis Validation Absolute value Cost Accessibility

15 Absolute Perfusion from Perfusion CT So et al. Int J Cardiovasc Imaging 2012;28:1237 Huber et al. Radiology 2013;269:378 Mahnken et al. Invest Radiol 2010;45:298

16 Absolute Perfusion from Perfusion MR Patlak Plot Method Kurita et al. Eur Heart J 2009;30:444 Tomiyama et al. J Mag Res Imaging 2015;42:754

17 Absolute Flow Measurement: 13 N-NH 3 Two-tissue compartment model (Michigan/UCLA) Hutchins et al. JACC 1990;15:1032 /Choi et al. JNM 1999;40:1045 One-tissue compartment model (Duke) De Grado et al. JNC 1996;3:494 C T (t) C P (t) K 1 k 2 C 1 Un-metabolized extravascular k 3 C 2 Metabolized C P (t) K 1 C T (t) k 2 K 1 equals the perfusion

18 Recent Advances of PET Imaging in CAD Instrument / Analysis Radiopharmaceuticals

19 Hybrid Imaging: SPECT/CT and PET/CT Kong et al. NMMI 2009

20 Multicenter Clinical Trial: EVINCI Software-based Fusion MPS and CTCA F/U by CAG and FFR Liga et al. Eur Heart J Cardiovasc Imaging Epub 2016

21 PET/MRI Philips Ingenuity TF PET/MR GE Signa PET/MR (Vendor image) Siemens mmr in SNUH

22 FDG PET/MRI in H-CMP 3.0 (SUV) (SUV) Kim KJ et al. Presented at KSC

23 FDG PET/MRI for Viability Assessment Nensa et al. Radiology 2015;276:400

24 Analysis Tools for Perfusion MBF module (Siemens) Carimas (Turku PET Centre) QPS (Cedars-Sinai) FlowQuant (U.O.) PMOD (PMOD Tech.) Corridor4DM (U.M./INVIA)

25 Myocardial Perfusion Tracers 201 Tl 99m Tc Agents 15 O-H 2 O 13 N-NH 3 82 Rb 18 F-Flurpiridaz T 1/2 73 h 6.01 h 122 sec 9.96 min 76 sec 110 min Photon Energy 70 kev 140 kev Positron Positron Positron Positron Uptake Mechanism Na/K Channel Diffusion Mitochondria Free Diffusion Diffusion - Glutamine Syn. Na/K Channel Diffusion Mitochondria Supply Pre-order Labeling Cyclotron Cyclotron Generator ( 82 Sr/ 82 Rb) (T 1/2 = 25 d) Cyclotron - Delivery (?) Dose (MBq) ,000 2, ,000 2, Exposure (msv) 12 msv (6 msv/mci) MIBI: 8 msv (0.4 msv/mci) TF: 5.6 msv (0.28 msv/mci) 2.4 msv (0.04 msv/mci) 1.5 msv (0.08 msv/mci) 3.8 msv (0.13 msv/mci) < 3 Current Status 30,600/mCi 68,000/0.25v 조제실제제 품목허가 / 조제실제제 FDA 승인국내미도입 해외임상 3 상 인정비급여 (2015) 도입추진중

26 Differences in Quantification Sciagra et al. Eur J Nucl Med Mol Imaging 2016 EPub

Study Protocol of 13 N-NH 3 PET 1. Rest : 10 min list-mode dynamic -1 CT 13 N-NH 3 10 mci 0 4 10 List mode acquisition for Q-CBF For static image recon.

27 Study Protocol of 13 N-NH 3 PET 1. Rest : 10 min list-mode dynamic -1 CT 13 N-NH 3 10 mci List mode acquisition for Q-CBF For static image recon. Dynamic Image Frame s 6 30 s 2 60 s Interval : > 30 min 3. Stress : 10 min list-mode dynamic A total of 1.6 msv from PET (Tl 2 mci + MIBI 15 mci: 15 msv) CT Adenosine 0.14 mg/kg/min 13 N-NH 3 10 mci List mode acquisition for Q-CBF For static image recon. Protocol Summary Scheduling & Cyclotron: 1 일 2 회생산 / 최대 4 명 / 평균 2 명검사 Room occupying time: 30 min (2회합계 ) Scanner occupying time: 25 min Administered radioactivity: 20 mci of 13 N-NH 3 Radiation dose: < 2 msv

28 Mean Range (mm) 82 Rb Perfusion PET Protocols An Example of Imaging Protocol ( 82 Rb) 82 Rb Injection System Al-Mallah et al. J Nucl Cardiol 2010;17: Rb N 11 C 18 F 68 Ga 15 O E max of Positron (MeV)

29 Absolute Perfusion Measurement Need for Quantification of Absolute Myocardial Perfusion Balanced ischemia General microvascular disorders, DM Absolute CFR Microvasculature of Myocardium Camici & Rimoldi. J Nucl Med 2009;50:1076

women when focal stenosis occurs Related to diffuse CAD/MVD

30 Microvascular Dysfunction in Women CAD in Women Atypical non-exertional angina with diffuse CAD High mortality in aged women when focal stenosis occurs Related to diffuse CAD/MVD Less focal and more diffuse/mvd Patel et al. JACC Cardiovasc Imag 2016;9:465

Imaging Targets of Vulnerable Plaque Arterial lumen Monocyte Fibrous cap Smooth muscle cell 68 Ga-fucoidan 99m Tc-antiVCAM-1 Adhesion molecule Endothelium Intima Tissue Macrophage 18 F-FDG 18 F-FDM

31 Imaging Targets of Vulnerable Plaque Arterial lumen Monocyte Fibrous cap Smooth muscle cell 68 Ga-fucoidan 99m Tc-antiVCAM-1 Adhesion molecule Endothelium Intima Tissue Macrophage 18 F-FDG 18 F-FDM 18 F-choline 11 C-PK Ga-DOTATATE 64 Cu-nanoparticle Proteolysis 99m Tc-RP805 Foam cell Lipid core Apoptotic cells 99m Tc-annexin V Hypoxia 18 F-FMISO Calcification Neoangiogenesis 68 Ga-RGD 18 F-gRGD 99m Tc-NC Zr-bevacizumab 18 F-fluoride Lee SJ and Paeng JC Kor J Radiol 2015;16:955

32 11 C-PK11195 PET in Human Imaging mechanism: TSPO (PBR; peripheral benzodiazepine receptor) expression on macrophages Gaemperli et al. Eur Heart J 2012;33:1902

33 18 F-gRGD PET in Human Beer et al. JACC Cardiovasc Imaging 2014;7:178

34 Calcification F-18 Fluoride PET Active calcification in coronary artery Dweck et al. JACC 2012;59:1539

35 18 F-Fluoride PET in Human Joshi et al. Lancet 2014;383:705

36 Approved Healthcare Technology in NM 신의료기술 / 약품품목허가내역 보험급여 2009 년이전 ( 약품품목허가 ) 18 F-FDG, 18 F-FLT, 18 F-FPCIT 18 F-FDG PET (2006 년 ) 2010 년 2011 년 ( 호 ) 동맥경유방사선색전술 ( 호 ) 18 F-NaF PET, 11 C-acetate PET 2012 년 ( 호 ) 18 F-FLT PET, 18 F- FPCIT PET ( 호 ) 123 I-FPCIT SPECT, 13 N-NH 3 PET ( 호 ) Radioiodine SPECT/CT 2013 년 ( 호 ) 11 C-methionine PET 2014 년 심의중 ( 약품품목허가 ) 223 Ra-chloride (Xofigo ) ( 호 ) 18 F-FDOPA PET ( 호 ) 68 Ga-DOTATATE PET 18 F-FMISO PET 등 ( 제한적급여 ) 18 F-NaF PET, 18 F-FPCIT PET, 123 I-FPCIT SPECT

37 Fluoride PET for Coronary Artery

38 Lee JM, Koo BK, et al. In Preparation

39 Summary: Prime Time or Not? Position of Perfusion PET in CAD Absolute flow measurement Lower radiation, shorter imaging time, and higher image quality Recent Changes in PET Imaging Enabling of clinical perfusion PET / prospect for more RP New technology: hybrid imaging and easy analysis tools Clinical evidences for needs of perfusion measurement However, still limited clinical availability and appropriate niche Future Direction Improvement in clinical availability Molecular imaging for risk stratification of CAD (?)

Treatment and Role of Hormaonal Replaement Therapy

Treatment and Role of Hormaonal Replaement Therapy Treatment and Role of Hormone Replacement Therapy Chung-Ang University Hospital Chee Jeong Kim 7.2 5.3 6.4 5.6 7.3 5.5 1 1 2 3 4 10 11 7 34 49 122 123 1.0 - - 10. 2001 1998 1998 Improvement of postmenopausal