PET Myocardial Perfusion Imaging: Protocols and Procedures George Segall, M.D. Stanford University

PET Perfusion Agents Diffusible tracers Radioisotope Form Half-life MeV Rubidium-82 (82Rb) Chloride 75 sec 3.15 Nitrogen-13 (13N) Ammonia 10 min 1.19 O-15 (15O) Water 110 sec 1.72 Copper-62 (62Cu) PTSM 9.8 min 2.94 Potassium-38 (38K) Chloride 7.6 min 2.70 Carbon-11 (11C) Butanol 20 min 0.96 PTSM, pyruvaldehyde methylthiosemicarbazone

Medicare Coverage Policy 1995 Rb-82 PET for myocardial perfusion 1998 F-18 deoxyglucose PET and SPECT for myocardial viability 2003 N-13 ammonia for myocardial perfusion

Medicare Coverage Policy for Rb-82 and N-13 ammonia PET whether at rest alone, or rest with stress, is approved when PET is • performed in place of SPECT, or • used following SPECT when results are equivocal, technically uninterpretable, or discordant with clinical care SPECT may not be used following an inconclusive PET

RAM License Strontium-82 200 mCi Rubidium-82 200 mCi Strontium-85 Generator contains 90-150 mCi of Sr-82 at time of calibration (package insert)

Rb-82 Infusion System

Relative Advantages Rb-82 N-13 ammonia Availability Excellent Limited Logistics Easy Difficult Cost Fixed Variable

Decision Analysis Occasional Imaging On-site cyclotron Daily Imaging N-13 ammonia and Daily Imaging PET/CT capacity Rb-82 chloride and

Decision Analysis Flexibility Convenience Exercise Regadenoson Adenosine N-13 ammonia Dipyridamole Dobutamine Convenience Regadenoson Rb-82 chloride Adenosine Dipyridamole

Scheduling N-13 ammonia Rb-82 chloride scheduled > 1D in advance √ • problematic cases inconclusive SPECT high BMI √ scheduled day of exam • ED and inpatients

Emission protocol N-13 ammonia • 20-30 mCi • 2D gated emission • start 10 min p injection Rb-82 chloride • 40-60 mCi • 2D gated emission • start 90 sec p injection

2D vs 3D Gated Rb-82 PET Knesaurek. BMC Nucl Med 2007;7:4 16 normal volunteers had resting Rb-82 on a BGO PET camera Low dose (20 mCi) 3D acquisition compared to high dose (60 mCi) 2D acquisition

Emission Reconstruction Rb-82 chloride • reconstruction filter: Butterworth 0.4 roll-off / power 10 • post reconstruction: axial smoothing N-13 ammonia • reconstruction filter: Butterworth 0.40 roll-off / power 10 • no post reconstruction smoothing

CT protocol • 140 keV • 30-210 mAs (noise index 25.0) • pitch 0.5 • ungated

PET Perfusion Agents •Rb-82 Chloride and N-13 ammonia are both extractable agents which passively diffuse across cell membranes •Both tracers have high first-pass myocardial extraction fractions, which are inversely related to flow is a non-linear manner.

Rb-82 chloride •Rb-82 is rapidly cleared from the circulation Tang. Phys Med Biol 2009;54:3161-3171 •Rb-82 is rapidly cleared from the circulation

N-13 ammonia •N13 is rapidly cleared from the circulation

N-13 ammonia •N-13 ammonia is trapped in the myocardium from the action of glutamate dehydrogenase1 and glutamine synthetase2 -ketoglutarate NH3 1 2 13NH4+ 13NH3 13NH3 glutamate glutamine glutamine urea

PET Perfusion Agents Relationship to CBF Rb-82 Chloride N-13 ammonia Bergman SR. In: PET of the Heart. Eds: Bergmann SR, Sobel BE. 1992 Schelbert Hr, Schwaiger M. In: PET and Autoradiography. Eds: Phelps ME, Mazziotta JC, Schelbert H 1986

Work Flow Rb-82 40-60 mCi min N-13 ammonia 20-30 mCi inject inject CT scan Pers scan 5 10 15 20 25 30 35 40 45 50 55 60 min CT scan Pers scan inject inject N-13 ammonia 20-30 mCi

Rb-82 chloride min inject inject CT scan Pers scan 5 10 15 20 25 30 35 5 10 15 20 25 30 35 40 45 50 55 60 min CT scan Aden scan inject inject

Rb-82 chloride min inject inject CT scan Pers scan 5 10 15 20 25 30 35 5 10 15 20 25 30 35 40 45 50 55 60 min CT scan Reg scan inject inject

N-13 ammonia min 5 10 15 20 25 30 35 40 45 50 55 60 inject scan Pers 5 10 15 20 25 30 35 40 45 50 55 60 inject scan Pers min CT 65 70 75 80 85 90 Ex •••

Injection times Cyclotron starts production 23 minutes prior to calibration time Ex Reg = inject Ad Per Dob 5 10 15 20 25 30 35 40 45 50 55 60

Normal Rb-82 perfusion study

Normal Rb-82 perfusion study

Normal Rb-82 perfusion study

Normal Rb-82 perfusion study

Abnormal Rb-82 perfusion study

Abnormal Rb-82 perfusion study

Normal N-13 perfusion study

Normal N-13 perfusion study

Abnormal N-13 perfusion study 72 year old man with peripheral vascular disease. Coronary arteriography: •LAD: 60% ostial and 80% mid vessel stenoses •LCX: 90% proximal stenosis and occluded OM •RCA: 90% ostial stenosis

Summary • PET myocardial perfusion protocols are simple and easy to incorporate in most practices • Rb-82 and N-13 ammonia are qualitatively equivalent

Summary • High throughput, and low cost per patient makes Rb-82 PET practical in a high volume practice • NH3-ammonia PET is better suited for occasional use in patients with inconclusive SPECT, or as the test of choice in problematic patients

3