Introduction to Nuclear Cardiology II Principles of Instrumentation and Radiopharmacy Matthew M. Schumaecker, MD, FACC Carilion Clinic / VTSOM Assistant Professor of Medicine

Objectives Become familiar with the terminology used in nuclear imaging Become familiar with the concepts underlying nuclear perfusion imaging Become familiar with 99m Tc and 201 Tl as radiopharmaceuticals Preliminary exposure to instrumentation, image acquisition and processing Tutorial: how to read a scan Become familiar with prognostic data associated with nuclear imaging

Corollary concepts Principles of nuclear physics Principles of risk stratification Principles of stress testing Principles of radiation safety PET imaging

MPI - The Basic Process 1. Radioisotope is injected into patient. 2. Radioisotope is taken up into certain cells. 3. Radioisotope decays emitting gamma-photons. 4. Gamma photons are detected by NaI/CZT crystal. 5. Gamma photons are transformed into visible photons by NaI/CZT crystal. 6. Visible photons are turned into electrons by a photomultiplier tube. 7. Electrons convert to digital signal.

MPI - The Basic Process Slide from E. Lindsay Tauxe ASNC, 7/2007

Compton Scatter and Collimators Collimators minimize compton scatter A lot of Compton Scatter

201 Thallium – Physical Properties Produced offisite by a cyclotron Physical t 1/2 = 73 hours Biological t 1/2 = 10 days Principal photon energies = kEV Prolonged half life limits total dose to 2- 4mCi

201 Thallium Monovalent Cation Some uptake via active transport ATPase Na + K + Tl + Rb + K+K+ Tl+

201 Thallium - Redistribution Around 4% of the dose is rapidly taken up by the myocardium – this demonstrates coronary flow. After initial extraction, there is continuous exchange of thallium between myocyte and intracellular compartment – this demonstrates viability.

201 Thallium Advantages Widely used Less expensive than technetium High myocardial extraction fraction Good linearity of uptake vs. flow Disadvantages Long half-life limits maximal dose to 4.5 mCi Substantial portion of photons scatter Low-energy photons are easily attenuated

99m Technetium Also emits photons by gamma-decay T 1/2 is 6 hours ◦ This allows much higher dosing Higher photo peak (~140 kEV) ◦ This causes less photon scatter and attenuation Three 99m Tc agents are approved: 1.Sestamibi (Cardiolite) 2.Tetrofosmin (Myoview) 3.Teboroxime (Cardiotec) – not currently available

Sestamibi Lipophilic monovalent cation Na/K/ATPase pump not used Exact mechanism of myocardial uptake is unclear Appears to be passive across the plasma membrane and mitochondrial membrane Becomes sequestered in the mitochondria because of the negative membrane potential Therefore only minimal, if any, redistribution occurs with sestamibi.

Sestamibi Non-linearity of uptake vs. coronary flow Slide from Dr. Gary Heller ASNC, 7/2007

Sestamibi Advantages Higher dose can be given because of short half life Lack of redistribution – can obtain multiple images over several hours Can obtain perfusion imaging and gating in one study Disadvantages Non-linear extraction 60% first-pass extraction Lack of redistribution – need 2 injections; limited viability information Excretion in hepatobiliary system

Tetrofosmin Lipophilic, cationic diphosphine compound Similar uptake mechanism as Sestamibi Quick clearance from the liver Slow clearance from the heart

Sestambi vs Tetrofosmin Soman et. al

REVIEW Stress Modality: Dobutamine Beta agonist Simulates exercise by positive chronotropy and inotropy. Can be difficult to achieve 85% MPHR with dobutamine alone May need to augment chronotrophic response with atropine up to 1 mg. Can cause SAM and LVOT obstruction in patients with significant septal hypertrophy.

REVIEW Stress Modality: Vasodilator Slide by Dr. Robert Hendel. ASNC 7/07

REVIEW Stress Modality: Vasodilator Slide by Dr. Robert Hendel. ASNC 7/07

REVIEW Stress Modality: Adenosine Causes coronary arteriolar vasodilation Extremely short half life Given in a four or six minute infusion Tracer is injected halfway through the protocol Can cause flushing, diaphoresis, chest pain. Usually resolves within minutes after infusion

Stress Modality: Dipyridamole Trade Name: Persantine Acts by blocking the cellular uptake of adenosine Four to ten times less expensive than adenosine Comparable to adenosine with respect to sensitivity; specificity may be lower Much longer half life so adverse reactions tend to be more severe

0 = Normal 1 = Slight reduction of uptake 2 = Moderate reduction of uptake 3 = Severe reduction of uptake 4 = Absent uptake Segmental Scoring

Most outcome data uses old 20-segment model 0-4 Normal 4-8 Mildly abnormal 9-13 Moderately abnormal >13 Severely abnormal In 17-segment model >11 is severely abnormal

SPECT - Prognostic Value Slide from Dr. Robert Hendel ASNC, 7/2007

SPECT - Prognostic Value Slide from Dr. Robert Hendel ASNC, 7/2007

Gated Images - Prognostic Value Slide from Dr. Robert Hendel ASNC, 7/2007

SPECT vs. Direct Cath - Outcomes Slide from Dr. Robert Hendel ASNC, 7/2007

SPECT vs. Direct Cath - Outcomes Slide from Dr. Donna Polk ASNC, 7/2007

Attenuation Correction Slide from Dr. Robert Hendel ASNC, 7/2007

Attenuation Correction Slide from Dr. Robert Hendel ASNC, 7/2007

Attenuation Correction Slide from Dr. Robert Hendel ASNC, 7/2007

Special Considerations Slide from E. Lindsay Tauxe ASNC, 7/2007

Cardiac SPECT - Conclusions Excellent prognostic information ◦ Can tell likelihood of angiographically significant CAD and ◦ Likelihood of a cardiac event ◦ Negative study is very powerful ◦ LV function data Excellent diagnostic accuracy ◦ With all tracers and stress modalities ◦ Additive benefit of supine/prone ◦ Additive benefit of attenuation correction Safe and cost-effective gatekeeper to the cath lab