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Primer on Cardiac Imaging THE UNIVERSITY OF NEW MEXICO HEALTH SCIENCES CENTER COLLEGE OF PHARMACY ALBUQUERQUE, NEW MEXICO Correspondence Continuing Education Courses for Nuclear Pharmacists and Nuclear Medicine Professionals VOLUME 11, LESSONS 2 AND 3 Primer on Cardiac Imaging By Richard J. Kowalsky, Pharm D, BCNP, FAPhA University of North Carolina The University of New Mexico Health Sciences Center College of Pharmacy is accredited by the Accredication Council for Pharmacy Education as a provider of continuing pharmaceutical education. Program No. 039-000- 04-003-H04. 5.0 Contact Hours or .50 CEUs. Expires 05/25/2007. 2 Primer on Cardiac Imaging By: Richard J. Kowalsky, Pharm D, BCNP, FAPhA Coordinating Editor and Director of Pharmacy Continuing Education William B. Hladik III, MS, RPh College of Pharmacy University of New Mexico Health Sciences Center Managing Editor Julliana Newman, ELS Wellman Publishing, Inc. Albuquerque, New Mexico Editorial Board George H. Hinkle, MS, RPh, BCNP, FASHP, FAPhA David Lawrence Laven, NPh, CRPh, FASHP, FAPhA Jeffrey P. Norenberg, MS, PharmD, BCNP, FASHP Neil A. Petry, MS, RPh, BCNP, FAPhA Timothy M. Quinton, PharmD, MS, RPh, BCNP, FAPhA Guest Reviewer Nicki L. Hilliard, PharmD, MHSA, BCNP, FAPhA Associate Professor of Nuclear Pharmacy University of Arkansas College of Pharmacy 4301 W. Markham, Slot 522 Little Rock, AR 72205 While the advice and information in this publication are believed to be true and accurate at press time, the author(s), editors, or the publisher cannot accept any legal responsibility for any errors or omissions that may be made. The publisher makes no war- ranty, expressed or implied, with respect to the material contained herein. Copyright 2004 University of New Mexico Health Sciences Center Pharmacy Continuing Education Albuquerque, New Mexico 3 PRIMER ON CARDIAC IMAGING STATEMENT OF OBJECTIVES Upon completion of this lesson, the reader should be able to: 1. Explain the physiologic basis of myocardial perfusion imaging. 2. Compare and contrast the radiopharmaceuticals used in myocardial perfusion imaging. 3. Compare and contrast the methods used to induce cardiac stress in myocardial perfusion im- aging. 4. Describe the methods used to perform myocardial perfusion imaging. 5. List the agents used to induce pharmacologic stress and discuss their side effects, precau- tions, and limitations of use. 6. Describe the radiopharmaceuticals and methods used in myocardial ventriculography studies. 7. Describe the biochemical mechanisms involved with radiopharmaceuticals used in myocar- dial viability and metabolism studies. 8. Describe the mechanisms of localization of radiopharmaceuticals used in myocardial perfu- sion imaging and infarct-avid imaging. 9. Describe the strengths and limitations of SPECT and PET myocardial imaging agents for the diagnosis of heart disease. 4 COURSE OUTLINE INTRODUCTION MYOCARDIAL IMAGING MYOCARDIAL BLOOD FLOW VIABILITY CARDIAC STRESS METHODOLOGY Exercise Stress Pharmacologic Stress Adenosine Dipyridamole Dobutamine Precautions, Side Effects, and Contraindications MYOCARDIAL EXTRACTION SPECT RADIOPHARMACEUTICALS Thallous Chloride Tl 201 Injection Technetium Tc 99m Sestamibi Injection Technetium Tc 99m Tetrofosmin Injection Technetium Tc 99m Teboroxime Injection Technetium Tc 99m NOEt PET RADIOPHARMACEUTICALS PET Perfusion Agents Ammonia N 13 Injection Rubidium Chloride Rb 82 Injection Water O 15 Injection PET METABOLISM AGENTS 5 Fludeoxyglucose F 18 Injection Carbon C 11 Palmitate Sodium Acetate C 11 Injection VIABILITY ASSESSMENT BLOOD POOL IMAGING AGENTS Technetium Tc 99m Red Blood Cells In Vitro Method In Vivo Method Modified In Vivo Method Labeling Mechanism of Tc Red Blood Cells GATED EQUILIBRIUM RADIONUCLIDE VENTRICULOGRAPHY INFARCT-AVID IMAGING AGENTS Technetium Tc 99m Pyrophosphate Indium In 111 Imciromab Pentetate Technetium Tc 99m Glucaric Acid Technetium Tc 99m Annexin V REFERENCES QUESTIONS 6 PRIMER ON CARDIAC IMAGING By Richard J. Kowalsky, Pharm D, BCNP, FAPhA University of North Carolina In more recent years positron emission INTRODUCTION tomography (PET) imaging has commanded Cardiac imaging has played a key role in a greater role in cardiac imaging due to the the diagnostic workup of patients with heart establishment of cyclotrons in regional nu- disease. The use of radiotracers in nuclear clear pharmacies and PET cameras in nu- medicine for the diagnosis of heart disease clear medicine facilities. Fluorodeoxyglu- began its major development in the 1970’s. cose labeled with fluorine-18 (18F-FDG) is a During this time agents were introduced for glucose metabolism agent which is princi- infarct-avid imaging and myocardial perfu- pally used for assessing myocardial viabil- sion imaging. Initially, infarct-avid imaging ity, while 13N-ammonia and 82Rb-rubidium 99m with Tc-pyrophosphate, was widely used. chloride are used for measuring myocardial It provided an important contribution to the perfusion. Other PET agents, such as 11C- workup of patients who sustained an acute acetate and 11C-palmitate, are used in the cardiac event because at the time there was a assessment of myocardial metabolism. lack of sensitive diagnostic tests for identify- The radiopharmaceuticals for heart im- ing MI. Today, serum enzyme assays, such aging fall into four main groups (1) blood as CK-MB, myoglobin, and troponin, can flow agents to evaluate coronary artery provide the necessary information soon after blood flow and ischemia, (2) blood pool the MI event. While infarct-avid imaging in agents to evaluate heart function, (3) infarct- nuclear medicine has declined over the avid agents for myocardial infarction, and years, perfusion imaging has expanded. (4) metabolism agents to assess myocardial 201 Thallous chloride Tl was introduced for viability and metabolic processes (Table 1). myocardial perfusion imaging in 1975 and has remained an important radiopharmaceu- MYOCARDIAL IMAGING tical for this application despite the later in- The goals of cardiac imaging in nuclear troduction of 99mTc-labeled complexes. medicine are broad, encompassing the as- 99mTc-sestamibi and 99mTc-tetrofosmin are sessment of the cardiac chambers, myocar- currently the major myocardial perfusion dial perfusion, metabolism, and infarction, agents used in single-photon emission com- with the major focus in current practice on puted tomography (SPECT) imaging. While the assessment of myocardial perfusion and these agents have significant imaging advan- ventricular function. Measurement of re- tages over thallium, such as improved image gional myocardial perfusion in humans has resolution and the ability to assess ventricu- clinical applicability for identifying ische- lar function, thallium is still used for myo- mia, defining the extent and severity of dis- cardial perfusion imaging and has an impor- ease, assessing myocardial viability, estab- tant role in the assessment of myocardial lishing the need for medical and surgical viability with SPECT. intervention (revascularization), and moni- toring the effects of treatment. 7 Table 1. Myocardial Imaging Agents SPECT Agents Application 99mTc-Red Blood Cells Blood Pool Markers 99mTc-Pyrophosphate Infarct Avid Agents 111In-Imciromab Pentetate* 99mTc-Glucaric Acid 99mTc-Annexin V 201Tl-Thallous Chloride Perfusion Agents 99mTc-Sestamibi 99mTc-Tetrofosmin 99mTc-Teboroxime* 99m Tc-Nitrido dithiocarbamate [Tc-N-(NOEt)2] PET Agents Application 82Rb-Rubidium Chloride Perfusion Agents 15O-Water 13N-Ammonia 11C-Acetate Metabolism Agents 11C-Palmitate 18F-Fludeoxyglucose (FDG) * No longer marketed in the U.S. (Reprinted by permission from Radiopharmaceuticals in Nuclear Pharmacy and Nu- clear Medicine. © 2004 by the American Pharmacists Association). The majority of clinical nuclear medi- lumen diameter eventually predisposes one cine studies today use SPECT methods for to myocardial ischemia, a condition where data acquisition; however, PET is increasing coronary blood flow decreases to a level be- as centers with these capabilities become low that needed to meet oxygen demand. In established. Approximately 30 to 60% of all advanced ischemic CAD, where blood flow nuclear medicine procedures involve cardiac and tissue oxygenation is so low that it can- studies. The majority (~84%) of these studies not sustain cardiac function at rest, myocar- involve myocardial perfusion imaging, 15% dial infarction results and the affected tissue are for radionuclide ventriculography, and the dies. Clinically, it is important to distinguish remainder are for miscellaneous studies, e.g., between ischemic and infarcted myocardium infarct imaging and metabolism studies.1 because ischemic, and therefore, viable Myocardial perfusion imaging provides in- myocardium can be restored to health by formation regarding coronary artery blood medical and surgical intervention. flow, an indirect measure of oxygenation and Resting myocardial blood flow to most metabolism in the myocardium, while ven- regions of the left ventrical ranges from 0.6 triculography studies provide information to 0.8 mL/min/g.3 At rest, the oxygen extrac- about cardiac function. tion efficiency of the heart is about 70%, compared with 20% for skeletal muscle.4 MYOCARDIAL BLOOD FLOW Consequently, an increased myocardial oxy- Coronary artery disease (CAD) arises gen demand necessitates increased coronary principally from a gradual narrowing of blood flow. Coronary blood flow can in- coronary arterial lumen due to atheroscle- crease in almost direct proportion to the rotic deposits. The progressive narrowing of metabolic
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