Article Figures & Data
Figures
- FIGURE 1.
Dual-tracer SPECT imaging of postmyocardial infarction angiogenesis in a canine model using 111I-RP748, an αvβ3 integrin–targeted agent. Shown are in vivo 111In-RP748 SPECT images acquired at 20 and 45min after tracer administration (top 2 rows), 99mTc-sestamibi images (third row), and fused 99mTc-sestamibi (green) and 45-min 11In-RP748 (red) images (bottom row) in a dog 3 wk after left anterior descending coronary artery occlusion. 99mTc-sestamibi perfusion images demonstrate anterior perfusion deficit (yellow arrows). 111In-RP748 images demonstrate corresponding increased uptake in hypoperfused region (white arrows). Authors demonstrate that 4-fold increase in 111In-RP748 uptake in infarct region corresponds to increased αvβ3 expression and histologic evidence of angiogenesis. LV = left ventricle; MIBI = sestamibi; RV = right ventricle; VLA = vertical long axis; HLA = horizontal long axis. (Reprinted with permission of (8).)
- FIGURE 2.
Schematic representation of myocardial uptake of various PET and SPECT perfusion radiotracers in relation to coronary blood flow. Background colors in figure show typical ranges of myocardial blood flow during rest (peach), exercise stress (blue), and pharmacologic vasodilator stress (green). 15O-H2O displays nearly linear uptake over physiologic range of blood flow but has limited clinical utility because of suboptimal imaging characteristics. 18F-flurpiridaz maintains high levels of myocardial extraction at stress-level blood flows, and its uptake-flow curve thus demonstrates only minimal deviation from linearity. By contrast, 99mTc-sestamibi and 99mTc-tetrofosmin have more significant reductions in myocardial extraction at moderate and high blood flow rates, and their uptake-flow curves demonstrate significant deviations from linearity. 201Tl, 13N-NH3, and 82Rb have intermediate uptake-flow properties. (Reprinted from (18).)
- FIGURE 3.
Representative rest–stress 99mTc-SPECT and 18F-flurpiridaz PET images in patient with small heart. Images were acquired in 66-y-old woman with left ventricular end diastolic volume of 82 mL. Reversible anterior perfusion defect is more evident in 18F-flurpiridaz PET images (B) than 99mTc-SPECT images (A) and is consistent with 82% stenosis of left anterior descending coronary artery that was found on invasive coronary angiography. Greater sensitivity of 18F-flurpiridaz PET for detection of myocardial ischemia partially relates to its greater spatial resolution and more linear uptake over physiologic range of blood flow. (Reprinted from (17).)
- FIGURE 4.
Representative 123I-CMICE-013 SPECT perfusion images in a porcine model with left anterior descending coronary artery occlusion during dipyridamole stress. Images were acquired 15 min after injection and provide clear definition of occluded region. (Reprinted from (22).)
- FIGURE 5.
Presynaptic sympathetic imaging with 18F-FBBG PET. Figure shows representative sequence of whole-body 18F-FBBG coronal PET images in healthy volunteer. Myocardial signal persists after clearance from liver and surrounding organs. (Reprinted from (55).)
- FIGURE 6.
Pre- and postsynaptic sympathetic imaging with 11C-HED and 11C-CGP 12177 PET. Short axis 11C-HED and 11C-CGP 12177 PET images of patient with congestive heart failure. Significant pre- and postsynaptic mismatch are noted by arrows. (Reprinted from (49).)
Tables
Clinical field Unmet need Heart failure and cardiomyopathies Heart failure with preserved ejection fraction: phenotypic characterization, therapeutic development Heart failure with reduced ejection fraction: prognostication, precision approaches to therapy Post–myocardial infarction remodeling: prognostication Immunotherapy/chemotherapy-related cardiotoxicity: prediction, early recognition, prognostication, and assessment of treatment response Cardiac amyloidosis: single-scan diagnosis and typing (light-chain amyloidosis vs. transthyretin amyloidosis) Cardiac sarcoidosis: reduce dependence on dietary preparation, differentiate from other types of myocarditis/nonspecific uptake Genetic cardiomyopathies: risk stratification in asymptomatic or phenotype-negative carriers and those carrying variants of unknown significance Cardiac fibrosis: reproducible quantification, distinguish between active and stable disease Left ventricular assist devices: prediction of left ventricular myocardial recovery New medical therapies (e.g., angiotensin receptor neprilysin inhibitors, sodium glucose cotransporter 2 inhibitors): determination of mechanism of action, track therapeutic response Arrhythmias Sudden cardiac death: risk stratification, prediction of implantable cardiac defibrillator benefit Genetic arrhythmia syndromes: risk stratification in asymptomatic or phenotype-negative carriers and those carrying variants of unknown significance Atrial fibrillation: patient selection for ablation/cardioversion/antiarrhythmic drugs Valvular disease Valvular regurgitation/stenosis: determination of risk for progression, prediction of optimal timing of interventions, selection for medical therapy, tracking of therapeutic response Endocarditis or device infections: detection Vascular disease Atheroma: risk stratification Aortic aneurysm: risk stratification, prediction of endoleak Thrombosis or embolization: whole-body detection, determination of chronicity Perfusion: high-spatial-resolution imaging with absolute blood flow quantification, hybrid perfusion/angiographic imaging Peripheral artery disease: risk stratification, prediction of interventional benefit Application Radiotracer Mechanism/target Status Reference Perfusion 18F-flurpiridaz Mitochondrial complex 1 Phase 3 clinical (10,13–16) 18F-rhodamine 6G Mitochondrial membrane voltage sensor Initial clinical evaluations (20) 18F-fluorophenyltriphenylphosphonium Mitochondrial membrane voltage sensor Initial clinical evaluations (21) 123I-CMICE-013 Mitochondrial complex 1 Initial clinical evaluations (22) 123I-ZIROT Mitochondrial complex 1 Preclinical (23) Neuronal signaling Presynaptic 123I-MIBG Norepinephrine transporter FDA-approved for prognostication in heart failure (35,38,39,45,61) 11C-HED Norepinephrine transporter Clinical evaluations (34,36,37,48,49) 11C-epinephrine Norepinephrine transporter Initial clinical evaluations (48) 11C-phenylephrine Norepinephrine transporter Initial clinical evaluations (48) 18F-FBBG Norepinephrine transporter Initial clinical evaluations (54,55) 18F-4F-MHPG, 18F-3F-PHPG Norepinephrine transporter Initial clinical evaluations (58) 18F-MFBG Norepinephrine transporter Initial clinical evaluations (56,57) Postsynaptic 11C-CGP-12177, 11C-CGP-12388 β-receptor antagonists Initial clinical evaluations (37,49,59–61) 11C-GB67 α1-receptor antagonist (prazosin analog) Initial clinical evaluations (63,64) Parasympathetic 11C-donepezil Acetylcholinesterase antagonist Initial clinical evaluations (65) 11C-methylquinuclidinyl benzilate Muscarinic receptor antagonist Initial clinical evaluations (40) 2-deoxy-2-18F-fluoro-d-glucose-A85380 Selective α4β2 nicotinic receptor agonist Initial clinical evaluations (67) 18F-fluoroethoxybenzovesamicol Vesicular acetylcholine transporter Initial clinical evaluations (69) 18F-4F-MHPG = 4-18F-fluoro-meta-hydroxyphenethylguanidine; 18F-3F-PHPG = 3-18F-fluoro-para-hydroxyphenethylguanidine; FDA = Food and Drug Administration.
- TABLE 3
Properties of SPECT and PET Radionuclides with Existing or Potential Applications in Cardiovascular Imaging (9,12,70)
Radionuclide Production Half-life Decay (%) Eβ+ max (MeV) Rβ+ mean (mm) Eγ (MeV) γ-emitters (SPECT) 99mTc Generator (99Mo) 6.0 h IT (88), IC — — 0.141 201Tl Cyclotron 73.1 h EC — — 0.068–0.083* 123I Cyclotron 13.2 h EC (87), IC — — 0.159† Pure positron emitters (PET) 15O Cyclotron 2 min β+ (99.9) 1.732 3.0 — 13N Cyclotron 10.0 min β+ (99.8) 1.199 1.8 — 11C Cyclotron 20.4 min β+ (99.8) 0.960 1.2 — 18F Cyclotron 110 min β+ (96.9) 0.634 0.6 — Mixed emitters (PET) 64Cu Cyclotron 12.7 h β+ (17.5)/EC 0.653 0.7 — β− (38.5) — — — 89Zr Cyclotron 78.4 h β+ (22.7)/EC 0.902 1.3 0.909‡ 82Rb Generator (82Sr) 1.3 min β1+ (81.8) 3.378 7.1 — β2+ (13.1)/EC 2.601 5.0 0.777 68Ga Generator (68Ge) 68 min β1+ (87.7) 1.899 3.5 — β2+ (1.2)/EC 0.821 1.1 1.077 124I Cyclotron 100.2 h β1+ (11.7)/EC 1.535 2.8 0.602 β2+ (10.7) 2.138 4.4 — β3+ (0.3)/EC 0.812 1.1 0.723 EC — — 1.691 Eβ+ max = maximum energy of positrons; Rβ+ mean = mean range of positrons in water; Eγ = γ emission energy; IT = isomeric transition; IC = internal conversion; EC = electron capture.
↵*Nongaussian photopeak.
↵†Emits small proportions of high-energy γ-photons (>0.400 MeV) in addition to its primary emission at 0.159 MeV.
↵‡Does not behave as prompt γ because of long half-life of metastable intermediate.
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