ligands have high affinity for extrastriatal receptors and are displaced from the receptor sites by amphetamine-induced dopamine release (27,97,98). Even though dynamic receptor imaging has so far been used only for detection of striatal dopamine, it is theoretically possible to develop ligands that can detect release of other neurotransmitters in other brain areas. Such developments will go a long way in enhancing our under- standing of human cognitive control. Conclusion Neurotransmitter imaging has resulted in a considerable amount of new information concerning the pathogenesis of a number of neuro- logic and psychiatric conditions that include schizophrenia, addiction, Parkinson’s disease, Alzheimer’s disease, ADHD, epilepsy, anxiety, and affective disorders. Further, the use of these techniques in the diag- noses of subclinical Alzheimer’s and Parkinson’s disease in asympto- matic patients can help in early diagnosis and intervention. 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Badgaiyan 403 Section 4 Other Applications 22 Cardiovascular Applications Miguel Hernandez-Pampaloni An improved understanding of the pathophysiology of myocardial ischemia combined with the development of new diagnostic modali- ties has substantially modified the concepts of myoca rdial blood flow (MBF) and left ventricular function in coronary artery disease (CAD). Positron emission tomography (PET) has emerged as a unique tool to characterize physiologic and pathologic processes, and it already plays a significant role in different areas of clinical medicine, including car- diology. Cardiac PET is based on the properties of positron emitters and radiation detection to provide a noninvasive and in vivo assess- ment of regional myocardial perfusion and metabolism. Different study protocols have been largely used in the adult population to detect and grade the severity of coronary artery disease during the last two decades using cardiac PET technology. Further, cardiac PET using fluorine-18 ( 18 F) 2-fluoro-2-deoxyglucose (FDG) is considered the gold standard imaging modality for the assessment of myocardial viability (1) and is well recognized as providing accurate information on the long-term prognosis of the patients with chronic coronary ischemic disease (2). Positron emission tomography offers unique capabilities for nonin- vasive assessment of regional myocardial function and can disclose information of utmost importance for the more accurate understand- ing of pathophysiologic processes and for the optimal management of the diseased patient. By detecting the very early functional regional abnormalities before the development of more severe structural changes, PET imaging can be useful in providing improved and pre- ventive care to the patient. Thus, cardiac PET imaging can offer a more comprehensive understanding of the normal myocardial physiology and early recognition of functional abnormalities. This is even more important in pediatric cardiology where the early detection of myocar- dial dysfunction may be helpful in choosing the appropriate manage- ment for the prevention of long-term consequences. Recent surgical and technical advances in pediatric cardiology make even more impor- tant an accurate detection of potentially treatable coronary abnor- malities. Positron emission tomography imaging’s high spatial and 407 temporal resolution provides better image quality, especially important in small pediatric hearts, and it allows the quantification in absolute terms of the MBF and regional myocardial metabolism. Single photon emission computed tomography (SPECT) imaging quality is usually limited by poor resolution and the low usable activity of thallium 201 ( 201 Tl), whereas images obtained after the administration of technetium- labeled compounds are compromised by the high liver activity in close proximity to the small heart. This chapter describes the basic principles of PET applied to the study of the heart, and presents the current and potential future clini- cal applications of cardiac PET in pediatric patients. Principles of Emission Tomography Applied to the Cardiovascular System Positron emission tomography imaging features are based on the physical properties of the positron decay. A positron has the same characteristics as an electron, except for its positive charge. Positrons are emitted from unstable nuclei (that have an excess of protons) that dispose of their excess charge by emitting a positron. At the end of the positron range, after losing its kinetic energy, a positron combines with an electron and the two particles annihilate. The annihilation coinci- dence detection of the two colinear 511-keV gamma rays photons, emitted in diametrically opposite directions by opposing scintillator detectors, is the essence of the PET imaging formation (3). To detect the location of the annihilation event, detectors are placed on opposite sides of the source and are connected in a coincidence detection circuit. When a given event is recorded simultaneously, positron annihilation is assumed to have taken place on the line between the detectors, and hence the location can be accurately determined. Radiopharmaceuticals Cardiac PET studies are performed with radiopharmaceuticals speci- fically synthesized to assess determined cardiac functions or biochemi- cal processes and with radiopharmaceuticals that have applications in other disciplines. The radiolabeled positron-emitting tracers used in cardiac PET studies are produced by a cyclotron or by a generator system. Currently, different processes of the heart have been studied using different radiopharmaceuticals (Table 22.1). The radiation expo- sure to PET radiotracers is lower compared to other radionuclides used for nuclear cardiology studies (Table 22.2). Evaluation of Myocardial Blood Flow The development of suitable radiotracers and appropriate mathemati- cal models applied to PET imaging has been shown to allow for the noninvasive and accurate quantification of regional MBF. Different radiotracers have been used for measuring MBF, including nitrogen- 13–labeled ammonia ( 13 NH 3 ) (4–6), oxygen-15 ( 15 O)-labeled water ( 15 O- 408 Chapter 22 Cardiovascular Applications [...]... 11.00 0.0320 0.0 58 6.90 0.0130 0.041 4.90 0.0067 0.027 4.10 0.0043 0.019 0. 68 0.00 28 0.015 0.34 0.0022 Kidney Kidney Bladder wall Newborn (3.5 kg) 1-yr-old (10 kg) 5-yr-old ( 18 kg) 10-yr-old (31 kg) 15-yr-old (56 kg) Adult (70 kg) Dose equivalent per body weight 0.34 0 .89 12.22 0.43 7.67 0.14 0.30 5.44 0.07 0.20 4.56 0.05 0.14 0.76 0.03 0.11 0. 38 0.02 18 F-FDG 0.310 0.100 0.077 0.050 0.0 38 0.030 Bladder... inflammatory processes (35) Different technetium-99m (99mTc)-labeled compounds are being studied for potential clinical use in patients with FUO, such as 99mTc-hexamethylpropylene-amine-oxime (HMPAO)-labeled leukocytes (36), 99mTc-ciprofloxacin (37), and 99mTc-labeled monoclonal antibodies ( 38, 39) FDG -PET Scan Mechanisms of FDG Uptake by the Cells Currently, 1 8- uoro-2-deoxyglucose (FDG) is the most clinically... incorporation of the radiotracer into M Hernandez-Pampaloni Glucose (18F-FDG) Lactate Hexobinase Lactate Glucose-6-phosphate Pyruvate Glycogen Mitochondria PDH Triglycerides Phospholipids Acyl-Camitine Camitine TCA Acyl-CoA α-GP CPTI β-oxidation Acety1-CoA Acyl-CoA CO2 Myocyte Free Fatty Acids (11C-Palmitate) CO2 11C-Acetate CO2 Figure 22.1 Radiotracers that can be used by PET to investigate different myocardial... program for the evaluation of cardiac PET studies: initial results in the detection and localization of coronary artery disease using nitrogen-13–ammonia J Nucl Med 1993;34(6): 9 68 9 78 33 Tillisch J, et al Reversibility of cardiac wall-motion abnormalities predicted by positron tomography N Engl J Med 1 986 ;314(14) :88 4 88 8 34 Knuuti MJ, et al Myocardial viability: fluorine- 1 8- deoxyglucose positron emission... Cyclotron Generator Cyclotron 110 min 20 min 0.2 mm 0. 28 mm Cyclotron Cyclotron H2O) (7–9), the potassium analogue rubidium -8 2 (82 Rb) (10), copper-62 (62Cu)-pyruvaldehyde bis(N4-methylthio-semicarbazone (62Cu-PTSM) (11,12), gallium- 68 (68Ga)-labeled albumin microspheres (13), and potassium 38 (38K) (14) The choice of a specific radiotracer is finally frequently determined by different factors besides their physical... As a potassium analogue, 82 Rb is retained in the myocardium and equilibrates with the cellular potassium pool Because of the dependence on the flow rate and the metabolic state, Table 22.2 Dosimetry in cardiac pediatric nuclear medicine 99m Newborn (3.5 kg) 1-yr-old (10 kg) 5-yr-old ( 18 kg) 10-yr-old (31 kg) 15-yr-old (56 kg) Adult (70 kg) Critical organ 201 13 Tc-sestamibi Tl N-ammonia Effective dose... Currently, 13NH3, 15O-H2O, and 82 Rb are the most widely used PET perfusion tracers Generator-produced 82 Rb has the advantages of not requiring a cyclotron and having a very short half-life ( 78 seconds), making it attractive for one-session rest/stress imaging 82 Rb has a low first-pass myocardial extraction fraction (50% to 60%) that results in a nonlinear uptake in relation to blood flow, particularly at... 15O-labeled water and PET J Nucl Med 1999;40(11): 184 8– 185 6 10 Herrero P, et al Noninvasive quantification of regional myocardial perfusion with rubidium -8 2 and positron emission tomography Exploration of a mathematical model Circulation 1990 ;82 (4):1377–1 386 11 Tadamura E, et al Generator-produced copper-62-PTSM as a myocardial PET perfusion tracer compared with nitrogen-13–ammonia J Nucl Med 1996;37(5):729–735... (87 ) Therefore, equivocal radiographic findings can be accurately characterized with FDG -PET There is also increasing concern about the risk of radiation (88 ), radiocontrast-induced nephropathy (89 ), and allergic reactions (90) to patients imaged with CT Furthermore, FDG -PET is able to detect early inflammatory and infectious lesions when anatomic imaging modalities reveal no abnormalities (91) FDG -PET. .. Coll Cardiol 1 989 ;14(3):639–652 8 Araujo LI, et al Noninvasive quantification of regional myocardial blood flow in coronary artery disease with oxygen-15-labeled carbon dioxide inhalation and positron emission tomography Circulation 1991 ;83 (3) :87 5– 88 5 9 Kaufmann PA, et al Assessment of the reproducibility of baseline and hyperemic myocardial blood flow measurements with 15O-labeled water and PET J Nucl Med . 11.00 0.0320 0.310 1-yr-old (10kg) 0.0 58 6.90 0.0130 0.100 5-yr-old (18kg) 0.041 4.90 0.0067 0.077 10-yr-old (31kg) 0.0274.10 0.0043 0.050 15-yr-old (56kg) 0.019 0. 68 0.00 28 0.0 38 Adult (70 kg) 0.015. ( 82 Rb) (10), copper-62 ( 62 Cu)-pyruvaldehyde bis(N4-methylthio-semicarbazone ( 62 Cu-PTSM) (11,12), gallium- 68 ( 68 Ga)-labeled albumin microspheres (13), and potassium 38 ( 38 K) (14). The choice. kg) 0 .89 12 .22 0.34 1.64 1-yr-old (10kg) 0.43 7.67 0.14 0.69 5-yr-old (18kg) 0.30 5.44 0.07 0.41 10-yr-old (31kg)0.204.56 0.05 0.26 15-yr-old (56kg)0.14 0.76 0.03 0.20 Adult (70 kg)0.11 0. 38 0.02