海外研究留学報告 福島賢慈 東京女子医科大学 画像診断 核医学部 核医学地方会 2011 Jan

Transcription

1 2011 Jan

2 Maryland state (MD), USA

3 Maryland state (MD), USA

4 Baltimore city, MD

5 Baltimore city, MD

6 Myocardial Perfusion PET tracers PET Tracers Half life Production First Pass Extraction Kinetic Properties 13N Ammonia 10 min Cyclotron 85% Metabolic trapping 82Rb 76 sec Generator 65% Na/K ATPase channel 15O H 2 O 122sec Cyclotron 100% Freely diffusible 18F flurpiridaz 110 min Cyclotron or Delivery 90% Binds to mitochondrial complex-1 FDA approved Heart Fail Rev 2010

7 Protocol for Pharmacological stress with 82 Rb Myocardial Perfusion PET

8 Dypiridamole: 7min Adenosine: 3-4min Protocol for Pharmacological stress with 82 Rb Myocardial Perfusion PET

9 Dypiridamole: 7min Adenosine: 3-4min Rergadenoson (selective A2A agonist) Available for rapid infusion Less side effects Protocol for Pharmacological stress with 82 Rb Myocardial Perfusion PET

10 Case years Female w/ Chest pain Risk factors: HT, HLp, Smoking, Obese (108kg) Stress Rest Stress Rest Stress Rest 99m Tc-tetrofosmin (10 th Oct 2007) 82 Rb (16 th Oct 2007)

11 Case years Female w/ Short of breath Risk factors: HT, DM, Dialysis Stress Rest Stress Rest Stress Rest 99m Tc-tetrofosmin (17 th May 2009) 82 Rb (26 th May 2009)

12 Diagnostic accuracy of 82 Rb myocardial perfusion PET: comparison with 99m Tc sestamibi SPECT Bateman et al J Nucl Cardiol 2006

13 Prognostic value of 82 Rb myocardial perfusion PET Normal Rb perfusion Abnormal Rb perfusion Yoshinaga et al JACC 2006

14 Prognostic value of 82 Rb myocardial perfusion PET Courtesy; CME Cardiac PET

15 Courtesy; CME Cardiac PET

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18 18 F flurpiridaz (formerly BMS ) 18 F-BMS : analogue of the insecticide pytidaben Rat myocardium Pig heart Higuchi et.al JNM2008 Nekora et.al Circulation 2009

19 Clinical advantages of hybrid PET-CT for cardiac study Conventional analysis w/ CT based attenuation correction (Myocardial perfusion, cardiac function, and volume) Myocardial flow quantification GE Discovery 64 slice PETCT Cardiac CT (Coronary imaging, Plaque analysis, Calcium scoring and delayed image)

20 PET Tracer Uptake Vs. Myocardial Blood Flow Courtesy; CME Cardiac PET

21 Myocardial Flow Measurement with Dynamic PET Boogers, Fukushima et.al Heart Fail Rev 2010

22 Long term prognostic value of coronary flow reserve (CFR) by 13 N Ammonia Herzog, Husman et.al JACC 2009

23 Prognostic usefulness of myocardial flow reserve (MFR) by 82 Rb PET Perfusion Flow Reserve M Schwaiger, High lights lecture SNM2010

24 Prognostic usefulness of myocardial flow reserve (MFR) with normal perfusion by 82 Rb PET Stress Flow Flow Reserve Fukushima, Javadi et.al JNM 2011 in press

25 Routine utility Translation of Basic Science to Clinical Application Clinical study Clinical trial Large mammals Rabbit mouse rat Vivo imaging Conception Ex vivo imaging or Kinetics

26 Angiotensin II type 1 receptor imaging The angiotensin II type 1 receptor (AT1R) is the primary receptor of the RAAS in myocardium. Experimental studies suggest that it mediates proinflammatory, proapoptotic and profibrotic processes in maladaptive conditions. Clinically, it has been shown that AT1R blockade improves outcome after myocardial infarction. Carbon-11 labeled AT1R blocker

27 Imaging of cardiac RAS activation after myocardial infarction using rat model Myofibroblast Higuchi, Fukushima et.al JNM 2010

28 Imaging of cardiac RAS activation after myocardial infarction using rat model Higuchi, Fukushima et.al JNM 2010

29 Species variability of Myofibroblast expression in myocardial infarction Gallagher AM et.al Am J Physiol 1998

30 AT1R expression in pig model of myocardial infarction Van Katz JP et.al Circulation 2000

31 AT1R expression in pig model of myocardial infarction Van Katz JP et.al Circulation 2000

32 Experimental myocardial infarction Balloon occlusion C-Arm fluoroscopy (Siemence) Balloon occlusion LAD mid for min Reperfusion

33 Large animal study with clinical scanner

34 Healthy Animal 16.7KBq/mL 11 C KR31173 (AT1R) SA HL 0 MIP 13 NH 3 (Perfusion) Axial PET CT VL 130KBq/mL SA HL 0 MIP Axial PET CT VL CVC SNM2010 at Salt lake city

35 Binding Specificity with healthy pig 15MBq/ml 15MBq/ml 0 Control 0 Blocking (SK 1080, 2mg/kg iv) CVC SNM2010 at Salt lake city

36 PET CT After Myocardial Infarction CT Delayed Enhancement (Scar) SA VLA HLA 13 NH 3 (Perfusion) 115KBq/mL 0 11 C KR31173 (AT1R) 29KBq/mL 2weeks after MI 0 CVC SNM2010 at Salt lake city

37 Regional Analysis 11 C KR Retention 11 C-KR31173 Retention Index Ml Pig 8 ** (P<0.01 vs all others) * (P<0.01 vs all others) Control 2 0 Control Infarct Remote (Lateral) Ml Group M Schwaiger, High lights lecture SNM2010

38 Established in 2007 Honored by Dr. Wagner & Dr. Torizuka Sponsored by Nihon medi physics US $48000 for two years (approximately $8,000 every 3 months)

39 SNM Wagner Trizuka fellowship Colloquium Banquet SNM2010 at Salt lake city SNM2009 at Toronto Ca

40 Acknowledgement Research team Higuchi T, Javadi MS, Lautamaki R, Takuro I, Fung G, Bravo P, Rischpler C, Chen D, Flotats A, and Bengel FM PET center Voicu C, Ramos A, Merrill J, Willet M Cyclotron Ravert H, Mathews B, Dannals RB, Brown J Laboratory Xia J, Angels J, Lee L, and Wahl RL Veterinary surgeon stuff DiPaula A, Tunnin R Financial support SNM/ Nihon Medi physics Thank you!!

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