Positronen-Computertomographie: Eine neue Methode zur quantitativen Bestimmung von Stoffwechsel, Durchblutung und Funktion des Herzens

H. R. Schön; H. R. Schelbert; M. E. Phelps

doi:10.1055/s-0038-1623798

Nuklearmedizin - NuclearMedicine, Table of Contents

Nuklearmedizin 1983; 22(04): 171-180
DOI: 10.1055/s-0038-1623798

Originalarbeiten - Original Articles

Schattauer GmbH

Positronen-Computertomographie: Eine neue Methode zur quantitativen Bestimmung von Stoffwechsel, Durchblutung und Funktion des Herzens

I. Technische und experimentelle Grundlagen^[*] Positron Computed Tomography: A New Method for Quantitative Measurement of Cardiac Metabolism, Perfusion and Function of the HeartI. Technical and Experimental Details

Authors

H. R. Schön

Aus der UCLA School of Medicine, Divisions of Nuclear Medicine and Biophysics, and the Laboratory of Nuclear Medicine, University of California at Los Angeles, Los Angeles, California, U.S.A
H. R. Schelbert

Aus der UCLA School of Medicine, Divisions of Nuclear Medicine and Biophysics, and the Laboratory of Nuclear Medicine, University of California at Los Angeles, Los Angeles, California, U.S.A
M. E. Phelps

Aus der UCLA School of Medicine, Divisions of Nuclear Medicine and Biophysics, and the Laboratory of Nuclear Medicine, University of California at Los Angeles, Los Angeles, California, U.S.A

Abstract

Die Positronen-Computertomographie stellt eine neue Methode dar, mit der physiologische Prozesse in verschiedenen Organen auf molekularer Ebene qualitativ und quantitativ erfaßt werden. So eröffnet dieses „physiologische Tomographieverfahren” z. B. im Herz die Möglichkeit, regional den myokardialen Stoffwechsel, die myokardiale Perfusion sowie die globale und regionale Myokardfunktion auf nicht-invasive Weise zu messen. Dieser einzigartige Vorzug, gleichzeitig die gegenseitige Abhängigkeit der Parameter Perfusion, Stoffwechsel und Funktion voneinander zu untersuchen, wird zukünftig das Verständnis von physiologischen und pathophysiologischen Vorgängen im Herzen erweitern und eventuell eine neue Einsicht im Verständnis kardialer Erkrankungen gewähren. Da eine große Anzahl der Herzerkrankungen auf Störungen im zellulären oder metabolischen Bereich zurückgehen, könnte diese neue Methode besonders der Früherkennung und einer eventuell damit verbundenen frühzeitigen Therapie von Herzerkrankungen dienlich sein. Mit Verbesserungen auf dem Sektor der Instrumentierung sowie der Entwicklung neuer physiologischer Indikatoren und vor allem kleiner, generatorähnlicher Zyklotrone dürfte die Positronen-Computertomographie zukünftig in größeren Zentren breite klinische Anwendung finden.

Positron computed tomography represents a new method which permits qualitative and quantitative assessment of physiologic processes in different organs on a molecular basis. Thus this ‘physiologic imaging device’ enables noninvasive detection of regional myocardial metabolism, perfusion and global as well as regional myocardial function. The unique capability of simultaneous measurement of the interdependent parameters perfusion, metabolism and function will provide new insights in physiologic and pathophysiologic processes of the heart and, hence, in the understanding of heart disease. Since a great number of cardiac disorders is related to disturbances at the cellular and metabolic level, this new method may contribute to the early detection and eventually to an early treatment of heart disease. With improvements in instrumentation as well as the development of new physiologic indicators and small generator-like cyclotrons, positron computed tomography will become clinically more widespread in various medical centers.

Full Text

References

Literatur
R1 Allan R. M, Jones T, Rhodes C. C. G. et al. Quantitation of myocardial perfusion in man using ¹⁵oxygen and positron tomography. Am. J. Cardiol 47: 481 1981;
R2 Barrio J. R, Egbert J. E, Baumgartner F. J. Enzymatic synthesis of ¹³N, ^llC labeled amino acids and related tricarboxylic acid cycle intermediates. J. nucl. Med 22: 77 (Abstr.). 1981;
R3 Berkowitz S, Perille T, Lesch M. Anaerobic amino acid metabolism as a potential energy source in mammalian heart. Clin. Res 26: 219 (Abstr.). 1978;
R4 Budinger TΚ, Yano Y, Derenzo S. E. et al. ⁸²Rb myocardial positron emission tomography. J. nucl. Med 20: 603 (Abstr.). 1979;
R5 Budinger J. F, Yano Y, Derenzo S. E. et al. Infarction sizing and myocardial perfusion measurements using ⁸²rubidium and positron emission tomography. Am. J. Cardiol 45: 399 (Abstr.). 1980;
R6 Budinger T. F, Derenzo S. E, Huesman R. H. et al. Quantitative myocardial flow extraction data using gated ECT. J. nucl. Med. v21 16 (Abstr.). 1980;
R7 Cho Z. H, Cohen M. B, Singh M. et al. Performance and evaluation of the circular ring transverse axial positron camera (CRTAPC). In Medical Radionuclide Imaging. Vol. I 269-290 IAEA Vienna; 1977
R8 Cohen M. B, Spolter L, MacDonald N. et al. Sequential enzymatic synthesis and separation of ¹³N-L-glutamatic acid and ¹³N-L-alanine. Radiopharmaceuticals 184-188 1975;
R9 Cohen M. B, Spolter L, Chang C. C. et al. Enzymatic synthesis of ¹¹C-pyruvic acid and ¹¹C-L-lactic acid. Int. J. appl. Radiat. Isot 31: 45 1980;
R10 Gallagher B. M, Ansari A, Atkins H. et al. Radiopharmaceuticals. XXVII. ¹⁸F labelled 2-deoxy-2-fluoro-D-glucose as a radiopharmaceutical for measuring regional myocardial glucose metabolism in vivo: Tissue distribution and imaging studies in animals. J. nucl. Med 18: 990 1977;
R11 Gelbard A. S, Clarke L. P, McDonald M. J. Enzymatic synthesis and organ distribution studies with ¹³N-labeled Lglutamine and L-glutamic acid. Radiology 116: 127 1975;
R12 Gelbard A. S, Benua R. S, Reman R. E. et al. Imaging of the human heart after administration of L-(^I3N) glutamate. J. nucl. Med. (In press).
R13 (Goldstein R. A, Klein M. S, Welch H. J. et al. External assessment of myocardial metabolism with 11-C palmitate in vivo. J. nucl. Med 21: 342 1980;
R14 Gould K. L, Schelbert H. R, Phelps M. E, Hoffman E. J. Noninvasive assessment of coronary stenoses with myocardial perfusion imaging during pharmacologic coronary vasodilatation. Am J. Cardiol 43: 200 1979;
R15 Hack S. N, Eichling J. O, Bergmann S. T. et al. External quantification of perfusion. Circulation 59/60 (Suppl. II): 11-269 (Abstr.). 1979;
R16 Henze E, Egbert J, Barrio J. R. et al. Myocardial energy metabolism evaluated by single pass uptake and positron emission computed tomography of ¹³N and “C labeled amino acids. J. nucl. Med 22: P10 (Abstr.). 1981;
R17 Heymann M. A, Payne H. D, Hoffman J. I. E, Rudolph A. M. Blood flow measurements with radioNuclide-labeled particles. Prog, cardiovasc. Dis 20: 55 1977;
R18 Hnatowich D. J. Labeling of human albumin microspheres with ⁶⁸Ga. J. nucl. Med 17: 57 1967;
R19 Hnatowich D. J. A method for the preparation and quality control of ⁶⁸Ga radiopharmaceuticals. J. nucl. Med 16: 764 1975;
R20 Hoffman E. J, Phelps M. E, Weiss E. S. et al. Transaxial tomographic imaging of canine myocardium with ¹¹C-palmitic acid. J. nucl. Med 18: 57 1977;
R21 Hoffman E. J, Phelps M. E, Wisenberg G. et al. Electrocardiographic gating in positron emission computed tomography. J. Comput. Assist. Tomogr 3: 73 1979;
R22 Huang S. C, Phelps M. E, Hoffman E. J. et al. Noninvasive determination of local cerebral metabolic rate of glucose in man with (¹⁸F)-fluoro-2-deoxyglucose emission computed tomography: Theory and results. Am. J. Physiol 238 E 69. 1980;
R23 Huang S. C, Phelps M. E, Carson R. E. et al. Tomographic measurement of local cerebral blood flow in man with ¹⁵O water. J. cereb. Blood Flow Metab 1 (Suppl. 01) 531 1981;
R24 Huang S. C, Schwaiger M, Carson R. E. et al. An ¹⁵O water clearance method for quantitative regional myocardial blood flow measurements. J. nucl. Med 23: P69 1982;
R25 Ido R, Wan C. N, Fowler J. S. et al. Fluorination with F₂, a convenient synthesis of 2-deoxy-2-fluoro-D-glucose. J. org. Chem 42: 2341 1977;
R26 Klein M. S, Goldstein R. A, Welch M. J, Sobel B. E. External assessment of myocardial metabolism with ¹¹C palmitate in rabbit hearts. Am. J. Physiol 237: H 51 1979;
R27 Knust E. J, Kupfernagel C. h, Stöcklin G. Long-chain 18F fatty acids for the study of regional metabolism in heart and liver; odd-even effects of metabolism in mice. J. nucl. Med 20: 1170 1979;
R28 Machulla H. J, Stöcklin G, Kupfernagel C. h. et al. Comparative evaluation of fatty acids labeled with ¹¹C, ^34mCl, ⁷⁷Br, and ¹²³I for metabolic studies of the myocardium. J. nucl. Med 19: 298 1978;
R29 Mudge Jr G. H., Mills Jr R. M., Taegtmeyer H. et al. Alteration of myocardial amino acid metabolism in chronic ischemic heart disease. J. clin. Invest 58: 1185 1976;
R30 Myers W. G. ³⁸Radiopotassium for in vivo studies of dynamic processes. J. nucl. Med 14: 359 1973;
R31 Oram J. R, Bennetch S. L, Neely J. R. Regulation of free fatty acid utilization in isolated perfused rat heart. J. biol. Chem 248: 5299 1973;
R32 Phelps M. E, Hoffman E. J, Coleman R. E. et al. Tomographic images of blood pool and perfusion in brain and heart. J. nucl. Med 17: 603 1976;
R33 Phelps M. E, Hoffman E. J, Raybaud D. Factors which affect cerebral uptake and retention of ¹³NH₃ . Stroke 8: 694 1977;
R34 Phelps M. E, Hoffman E. J, Huang S. C. Physiologic tomography: A new approach to in vivo measure of metabolism and physiologic function. In Medical Radionuclide Imaging. Vol. I 233-253 IAEA, Vienna; 1977
R35 Phelps M. E. Emission computed tomography. Sem. nucl. Med 7: 337-365 1977;
R36 Phelps M. E, Hoffman E. J, Selin C. et al. Investigation of ¹⁸F-2-fluoro-2-deoxyglucose for the measure of myocardial glucose metabolism. J. nucl. Med 19: 1311 1978;
R37 Phelps M. E, Huang S. C, Hoffman E. J. et al. Tomographic measurement of local cerebral glucose metabolic rate in man with 2-(¹⁸F)-fluoro-2-deoxy-D-glucose: Validation of the method. Ann. Neurol 6: 371 1979;
R38 Phelps M. E, Huang S. C, Hoffman E. J. et al. Tomographic measurement of cerebral blood volume with ¹¹C labeled carboxy hemoglobin. J. nucl. Med 20: 329 1979;
R39 Phelps M. E, Schelbert H. R, Hoffman E. J. et al. Physiologic tomography of myocardial glucose metabolism, perfusion and blood pools with multiple gated acquisition. In Advances in Clinical Cardiology. Weiss H. W. Ed. Vol. I 373-393 Gerhard Witzstrock, New York: 1980
R40 Ratib O, Phelps M. E, Huang S. C. et al. Determination of myocardial glucose metabolic rate by positron computed tomography and ¹⁸fluoro deoxyglucose. J. nucl. Med 22: P p11 (Abstr.). 1981;
R41 Rau E. E, Shine K. L, Gervais A. et al. Enhanced mechanical recovery of anoxic and ischemic myocardium by amino acid perfusion. Am. J. Physiol 236: H 873 1979;
R42 Reivich M, Kuhl D. E, Wolf A. et al. Measurement of local cerebral glucose utilization in man with ¹⁸F-2-Fluoro-2-Deoxy-D-Glucose. Circ. Res 44: 127 1979;
R43 Rothlin M. E, Bing R. J. Extraction and release of individual free fatty acids by the heart and fat depots. J. clin. Invest 40: 1380-1386 1961;
R44 Sanborn T, Favin W, Berkowitz S. et al. Augmented conversion of aspartate and glutamate to succinate during anoxia in rabbit heart. Am. J. Physiol 237: H 535. 1979;
R45 Sasayama S. D, Franklin D, Ross J. et al. Dynamic changes in left ventricular wall thickness and their use in analysing cardiac function in the conscious dog. Am. J. Cardiol 38: 870-879 1976;
R46 Selwyn A. P, Allan R. M, Pike V. et al. Positive labeling of ischemic myocardium: A new approach in patients with coronary disease. Am. J. Cardiol 47: 481 (Abstr.). 1981;
R47 Selwyn A. P, Allan R. M, L’Abbate A. et al. Relation between regional myocardial uptake of ⁸²Rb perfusion: Absolute reduction of cation uptake in ischemia. Am. J. Cardiol 50: 112 1982;
R48 Sokoloff L, Reivich M, Kenney C. et al. The (¹¹C) deoxyglucose method for the measurement of local cerebral glucose utilization. Theory, procedure and normal values in conscious and anesthetized rats. J. Neurochem 28: 897-916 1977;
R49 Schelbert H. R, Phelps M. E, Hoffman E. J, Huang S. C, Selin C. E, Kuhl D. E. Regional myocardial perfusion assessed with ¹³N labeled ammonia and positron emission computerized axial tomography. Am. J. Cardiol 43: 209 1979;
R50 Schelbert H. R, Phelps M. E, Huang S. C, MacDonald N. S, Hansen H, Selin C, Kühl D. E. ^l3N ammonia as an indicator of myocardial blood flow. Circulation 63: 1259 1981;
R51 Schelbert H. R, Schön H. R, Huang S. C, Barrio J, Phelps M. E. Effects of substrate availability and acute ischemia on regional myocardial metabolism demonstrated nonivasively with ¹⁸F deoxyglucose, ¹¹C palmitic acid and positron computed tomography. In Nuclear Medicine and Biology. Proceedings of the Third World Congress of Nuclear Medicine and Biology. Raynaud C. Ed 2510-2513 Pergamon Press, Oxford; 1982
R52 Schelbert H. R, Henze E, Schön H. R, Keen R, Hansen H. W, Selin C, Huang S. C, Barrio J. R, Phelps M. E. ¹¹C palmitic acid for the non-invasive evaluation of regional myocardial fatty acid metabolism with positron computed tomography. III. In vivo demonstration of the effects of substrate availability on myocardial metabolism. 2Am. Heart J. (In press).
R53 Scheuer J, Olson R. E. Metabolism of exogeneous triglyceride by the isolated perfused heart. Am. J. Physiol 212: 301-307 1967;
R54 Schön H. R, Schelbert H. R, Robinson G, Najafi A, Huang S. C, Hansen H, Barrio J, Phelps M. E. ¹¹C labeled palmitic acid for the non-invasive evaluation of regional myocardial fatty acid metabolism with positron computed tomography. I. Kinetics of ¹¹C palmitic acid in normal myocardium. Am. Heart J 103: 532-547 1982;
R55 Schön H. R, Schelbert H. R, Najafi A, Hansen H, Huang S. C, Barrio J, Phelps M. E. ¹¹C labeled palmitic acid for the non-invasive evaluation of regional myocardial fatty acid metabolism with positron computed tomography. II. Kinetics of ¹¹C palmitic acid in acutely ischemic myocardium. Am. Heart J 103: 548-561 1982;
R56 Schön H. R, Schelbert H. R, Phelps M. E. Positronen-Computertomographie: Eine neue Methode zur quantitativen Bestimmung von Stoffwechsel, Durchblutung und Funktion des Herzens. II. Klinische Wertigkeit. Dtsch. med. Wschr. (im Druck).
R57 Stein O, Stein J. Lipid synthesis, intracellular transport and storage. J. cell. Biol 36: 63-77 1968;
R58 Ter-Pogossian M. M, Klein M. S, Markham J. et al. Regional assessment of myocardial metabolic integrity in vivo by positron emission tomography with “C-labeled palmitate. Circulation 61: 242 1980;
R59 Walsh W. E, Harper P. V, Resnekov L. et al. Noninvasive evaluation of regional myocardial perfusion in 112 patients using a mobile scintillation camera and intravenous ¹³nitrogen-labeled ammonia. Circulation 54: 226 1976;
R60 Ward B. J, Gloster J. A, Harris P. The incorporation and. distribution of ³H oleic acid in the isolated perfused guinea-pig heart: A biochemical and EM autoradiographic study. Tissue & Cell 11: 793-801 1979;
R61 Weiss E. S, Hoffman E. J, Phelps M. E. et al. External detection and visualization of myocardial ischemia with ¹¹Csubstrates in vitro and in vivo. Circ. Res 39: 24 1976;
R62 Weiss E. S, Ahmed S. A, Welch M. J. et al. Quantification of infarction in cross sections of canine myocardium in vivo with positron emission transaxial tomography and ¹¹Cpalmitate. Circulation 55: 66 1977;
R63 Wisenberg G, Schelbert H. R, Hoffman E. J. et al. In vivo quantitation of regional myocardial blood flow by positron emission computed tomography. Circulation 63: 1248 1981;