1. PET Tracers for Clinical Cardiac Imaging
Josef Machac, MD, FACC
Professor of Radiology
The Mount Sinai School of Medicine
New York, NY

3. Radiotracers for Clinical Cardiac PET Imaging
Myocardial perfusion/function
N-13 Ammonia
Cyclotron
Rubidium-82
Generator
Myocardial viability
F-18 Fluorodeoxyglucose (FDG)
The clinical PET landscape has changed dramatically over the past decade.
Nearly all metropolitan areas in North America now have at least one commercial FDG supplier.
A commercial rubidium-82 generator was FDA approved and commercially available at the beginning the the 90s, thus making a reliable source of racer for myocardial PET perfusion imaging, obviating the need for a cyclotron.

4. Radiotracers for Clinical Cardiac PET Imaging
Myocardial perfusion/function
N-13 Ammonia
Cyclotron
Rubidium-82
Generator
Myocardial viability
F-18 Fluorodeoxyglucose (FDG)
The clinical PET landscape has changed dramatically over the past decade.
Nearly all metropolitan areas in North America now have at least one commercial FDG supplier.
A commercial rubidium-82 generator was FDA approved and commercially available at the beginning the the 90s, thus making a reliable source of racer for myocardial PET perfusion imaging, obviating the need for a cyclotron.

5. American Society of Nuclear Cardiology
Injection and imaging with a myocardial imaging tracer at rest may produce decreased uptake in regions affected by myocardial infarction, or supplied by severely stenosed coronary arteries.
However, most coronary artery disease will be missed if imaging is performed only at rest.
American Society of Nuclear Cardiology

6. American Society of Nuclear Cardiology
Therefore vasodilation and increased blood flow is needed to unmask most clinically significant coronary disease lesions.
Vasodilation can be directly produced by intravenous adenosine and dipyridamole.
Vasodilation can also be accomplished by increasing demand, through exercise or inotropic agent like dobutamine or arbutamine, which increase constractility and heart rate. Because the patient needs to be situated inside the PET scanner during the Rb-82 injection, exercise is impractical. Thus, dobutamine and arbutamine are the best second-line agents, in patients who cannot tolerate the vasodilator drugs dipyridamole and adenosine because of asthma.
Either way, blood flow, and therefore tracer deposition is increased in myocardium supplied by healthy vessels, whereas blood flow is increased less in areas supplied by diseased arteries, producing relative defects.
In patients with multivessel disease and the presence of collateral, blood flow can even be shunted away from the diseased regions to the more normal regions, the so called “coronary steal syndrome”. Tracer deposition is then decreased in the absolute sense.
American Society of Nuclear Cardiology

7. Radiotracers for Clinical Cardiac PET Imaging
Myocardial perfusion/function
N-13 Ammonia
Cyclotron
Rubidium-82
Generator
Myocardial viability
F-18 Fluorodeoxyglucose (FDG)
The clinical PET landscape has changed dramatically over the past decade.
Nearly all metropolitan areas in North America now have at least one commercial FDG supplier.
A commercial rubidium-82 generator was FDA approved and commercially available at the beginning the the 90s, thus making a reliable source of racer for myocardial PET perfusion imaging, obviating the need for a cyclotron.

8. Cardiac PET Tracers Agent Physical Mean Production Extraction
half-life positron
range (mm)
N-13 NH3 9.9 min 0.7 cyclotron 70%
Rb sec generator 50-60%
F-18 FDG 110 min 0.2 cyclotron 1-3%

9. Cardiac PET Tracer Dosimetry
Agent Activity TEDE Critical Organ Dose
(mCi) (rem) (organ) (rem)
N-13 NH * Bladder 0.60**
Rubidium * Thyroid 7.0**
F-18 FDG * Bladder 5.9*
* ICRP 80 ** ICRP 53

11. Myocardial Tracer Kinetics
N-13 Ammonia
0-30s s s s s s s

12. N-13 Ammonia
Phelps et al, 1986

13. Extraction of N-13 NH3 and Rb-82
Schelbert et al, Circulation 63: , 1981
Goldstein et al, J Nucl Med 24: , 1983
Yoshida et al, J Nucl med 37: , 1996

14. N-13 Ammonia
UCLA School of Medicine

15. N-13 Ammonia Advantages Disadvantages Good quality images
10 min half-life
Short positron travel
Good blood flow quantification capability
Can be used with pharmacological stress or exercise
Disadvantages
Need for on-site cyclotron production
Ties up cyclotron and manpower
Difficult logistics
Production-Imaging
10min half-life
Need for
Decay between rest and stress doses (20/20mCi)
Differential doses (10/30mCi)

16. Radiotracers for Clinical Cardiac PET Imaging
Myocardial perfusion/function
N-13 Ammonia
Cyclotron
Rubidium-82
Generator
Myocardial viability
F-18 Fluorodeoxyglucose (FDG)
The clinical PET landscape has changed dramatically over the past decade.
Nearly all metropolitan areas in North America now have at least one commercial FDG supplier.
A commercial rubidium-82 generator was FDA approved and commercially available at the beginning the the 90s, thus making a reliable source of racer for myocardial PET perfusion imaging, obviating the need for a cyclotron.

17. Cardiac PET Tracers Agent Physical Mean Production Extraction
half-life positron
range (mm)
N-13 NH3 9.9 min 0.7 cyclotron 70%
Rb sec generator 50-60%
F-18 FDG 110 min 0.2 cyclotron 1-3%

18. Cardiac PET Tracer Dosimetry
Agent Activity TEDE Critical Organ Dose
(mCi) (rem) (organ) (rem)
N-13 NH * Bladder 0.60**
Rubidium * Thyroid 7.0**
F-18 FDG * Bladder 5.9*
* ICRP 80 ** ICRP 53

19. Rubidium-82 Generator
Courtesy of Bracco Diagnostics

20. Rubidium-82 Generator
Courtesy of Bracco Diagnostics

21. Mount Sinai Clinical PET Center

23. Cardiac Rubidium-82 Kinetics
The Mount Sinai School of Medicine

24. The Mount Sinai School of Medicine
An 8 frame, 8 minute dynamic acquisition is made. The serial images are corrected for isotope decay.
Myocardial and blood pool time activity curves are generated.
The Mount Sinai School of Medicine

25. Clinical Case-KC Stress Rest Stress Rest Stress Rest Stress Rest
The stress images show LV cavity dilatation, and decreased perfusion everywhere except for the anterior basal segment.
The resting images appeared normal.
This is consistent with severe extensive ischemia.
Rest
Stress
Rest
Mount Sinai School of Medicine

26. Rubidium-82 Advantages Disadvantages Short half-life Always available
Challenge to:
PET cameras
Staff
Relatively long positron travel
Need for heavier filtering
More difficult quantification
Fixed cost of generator
Low volume
Advantages
Always available
No need for cyclotron
Efficient acquisition logistics
Short half-life
Can be repeated multiple times
If technical difficulties
Multiple stress interventions
Fixed cost of generator
High volume

27. Maximizing Obtained Dose from a Rb-82 Generator*
Because of the 75 sec half-life of Rb-82, obtaining maximum activity from the generator is important. Images may suffer from noise at the end of generator lifespan.
We investigated conditions predicting maximal Rb-82 activity, at various points of generator age, compared to fixed conditions and to maximal activity (PredMax) predicted from Sr-82 decay.
Kim, Machac, Almeida, Clin Nucl Med 29: 135P, 2004

28. Obtainable Rb-82 Activity
Condition A : Fixed Settings
Value Day1 D7 D D D24
Dial Activity
Dial Volume
Effective Act
Pred Activity
El Vol
ElTime
Kim, Machac, Almeida, Clin Nucl Med 29: 135P, 2004

29. Obtainable Rb-82 Activity
Condition B: Variable Settings
Value Day1 D7 D D D24
Dial Activity
Dial Volume
Effective Act
Pred Activity
Elution Vol
Elution Time
Kim, Machac, Almeida, Clin Nucl Med 29: 135P, 2004

30. Kim, Machac, Almeida, Clin Nucl Med 29: 135P, 2004

31. Conclusions: Maximizing Obtained Dose from a Rb-82 Generator
Maximal Effective Activity could be augmented only in the first week by increasing Dialed Activity.
Increasing Dial Volume usually diminished Effective Activity.
Effective Activity generally followed Predicted Maximum based on Sr-82 decay.
Elution Time reached a plateau after Day7-Day13.
Overall, optimizing Effective Activity has only marginal benefit after first week of generator life.
Kim, Machac, Almeida, Clin Nucl Med 29: 135P, 2004

32. Quantification of Myocardial Perfusion Compartmental Models
Clinically available PET imaging tracers
N-13 ammonia for centers with cyclotron
Rb-82 generator for centers without cyclotron

33. Radiotracers for Clinical Cardiac PET Imaging
Myocardial perfusion/function
Rubidium-82
Generator
N-13 Ammonia
Cyclotron
Myocardial viability
F-18 Fluorodeoxyglucose (FDG)
The clinical PET landscape has changed dramatically over the past decade.
Nearly all metropolitan areas in North America now have at least one commercial FDG supplier.
A commercial rubidium-82 generator was FDA approved and commercially available at the beginning the the 90s, thus making a reliable source of racer for myocardial PET perfusion imaging, obviating the need for a cyclotron.

35. Cardiac PET Tracers Agent Physical Mean Production Extraction
half-life positron
range (mm)
N-13 NH3 9.9 min 0.7 cyclotron 70%
Rb sec generator 50-60%
F-18 FDG 110 min 0.2 cyclotron 1-3%

36. Cardiac PET Tracer Dosimetry
Agent Activity TEDE Critical Organ Dose
(mCi) (rem) (organ) (rem)
N-13 NH * Bladder 0.60**
Rubidium * Thyroid 7.0**
F-18 FDG * Bladder 5.9*
* ICRP 80 ** ICRP 53

37. F-18 FDG Kinetics
Mount Sinai School of Medicine

38. F-18 FDG Kinetics
The Mount Sinai School of Medicine

39. Myocardial FDG Uptake During Fasting
The Mount Sinai School of Medicine

40. Myocardial FDG Uptake after Glucose Loading
The Mount Sinai School of Medicine

41. PET Viability Imaging Rest perfusion imaging
(Rb-82, N-13 ammonia, Tl-201, MIBI, Tetrofosmin)
Stress perfusion imaging (if possible)
Glucose management
Injection of F-18 FDG
Wait 60 minutes
Gated FDG imaging
The imaging protocol starts with overnight fasting.
The patient undergoes resting perfusion imaging with Rb-82 as with the normal perfusion protocol.
Whenever possible, we try to perform pharmacological stress Rb-82 perfusion imaging, in order to unmask stress-induced ischemia.
On the same day or a separate day, this is followed by FDG PET imaging.
This begins with glucose management. Numerous protocols have been published, using either oral or IV glucose loading, along with subcutaneous or IV insulin. We use IV glucose loading followed by IV insulin.
The patient is then injected with FDG intravenously.
The patient rests for 1 hour.
The patient then undergoes gated PET imaging, followed by a trasmission scan.

42. Gated FDG PET Imaging
Clicking on any of the image panels activates the cine display.

43. Standardization of Myocardial F-18 FDG Uptake
Oral glucose loading
IV bolus glucose loading
Euglycemic-Hyperinsulinemic Clamp
Niacin (Nicotinic Acid Derivative)
Guidelines for patient preparation and data acquisition:
J Nucl Cardiol 10: , 2003

44. * check blood glucose prior to deoxyglucose injection,
Oral Glucose Loading
Blood Glucose One Hour Before 18F-deoxyglucose administration
< 110 mg/dl Give 50 to 100g Glucose orally *
110 to 126 mg/dl No Glucose
> 126 mg/dl about 4 to 6 IU Regular Short-Acting Insulin IV.
Repeat blood glucose after 15 min for > 15% decrease;
If not, repeat Insulin IV
* check blood glucose prior to deoxyglucose injection,
if very high, insulin
UCLA School of Medicine

45. Rb-82 and F-18 FDG images in a diabetic patient
The Mount Sinai School of Medicine

46. The Mount Sinai School of Medicine

47. Substrate Utilization of Normal and of Dysfunctional Myocytes
Free Fatty
Acid
Glucose
Lactic
Acid
Free Fatty
Acid
Glucose
Lactic
Acid
Normally Contracting
Myocyte
Reversibly Dysfunctional
Myocyte
UCLA School of Medicine

48. Clinical Case: JR (PET rest Rb-FDG)
The Mount Sinai School of Medicine

49. Can Rubidium-82 Kinetics Be Used for Myocardial Viability?

50. Rb-82 Kinetics and Viability
Gould et al. J Nucl Med 31: 1-9, 1990

51. Resting Rb-82 Washout Normal Mild-Mod Severe M RMM MM FDGns
P=0.007
P=0.05
Resting Rb-82 Washout
This graph shows the resting Rb washout rate within each of the categories.
In general, there was nearly complete overlap of washout values between the FDG match and mismatch groups within each Rb defect type, despite minimal differences between means.
There was a marginally greater washout for FDG-Rb mismatch in the Mild-Moderate Rb defect category.
There was no significant effect of FDG-Rb match or mismatch on resting Rb washout rate in the severe defect category.
Normal
Mild-Mod
Severe
Rest Rb-82
Almeida et al. J Nucl Med 44: P7, 2003

52. Rb-82 Kinetics and Viability
The Mount Sinai School of Medicine

53. The End