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Biochemical Parameters in Radiopharmaceutical Design

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Positron Emission Tomography of the Brain

Abstract

The advent of positron computed tomography (PCT) has permitted for the first time the noninvasive application of tracer kinetic principles to man for the assessment of local physiologic processes (Phelps 1981). This approach, referred to as physiologic tomography (Phelps et al. 1977), relies upon the selection of appropriate radiolabeled compounds to monitor specific biochemical processes and the development of tracer kinetic models for the measurement of these processes.

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References

  1. Arnstein HRV, Richmond MH (1964) Utilization of p-fluorophenylalanine for protein synthesis by the phenylalanine-incorporation system from rabbit reticulocytes. Biochem J 91: 340–346

    PubMed  CAS  Google Scholar 

  2. Barrio JR, MacDonald NS, Robinson GD et al. (1981) Remote, semiautomated production of 78F-labeled 2-deoxy-2-fluoro-D-glucose. J Nucl Med 22: 372–375

    PubMed  CAS  Google Scholar 

  3. Barrio JR, Egbert JE, Henze E et al. (1982 a) L[4–11C]aspartic acid: enzymatic synthesis, myocardial uptake and metabolism. J Med Chem 25: 93–96

    Google Scholar 

  4. Barrio JR, Phelps ME, Huang S-C et al. (1982b) Positron-emitting labeled L-amino acids for measurement of protein synthesis. Trans Am Nucl Soc 41: 17–18

    Google Scholar 

  5. Baumgartner FJ, Barrio JR, Henze E et al. (1981) 73N labeled L-amino acids for in vivo assessment of local myocardial metabolism. J Med Chem 24: 764–766

    Google Scholar 

  6. Berger G, Maziere M, Knipper R et al. (1979) Automated synthesis of 11C-labeled radiopharmaceuticals: imipramine, chlorpromazine, nicotine and methionine. Int J Appl Radiat Isot 30: 393–399

    Article  PubMed  CAS  Google Scholar 

  7. Bergin R, Carlström D (1968) Structure of the pyrocatecholamines. II. crystal structure of dopamine hydrochloride. Acta Crystallogr Sect B 24: 1506–1510

    Article  CAS  Google Scholar 

  8. Bessell EM, Foster AB, Westwood JH (1972) The use of deoxyfluoro-D-glucopyranoses and related compounds in a study of yeast hexokinase specificity. Biochem J 128: 199–204

    PubMed  CAS  Google Scholar 

  9. Bright HJ, Porter DJT (1975) Flavoprotein oxidases. D-Amino acid oxidase. In: Boyer PD (ed) The enzymes, 3rd ed, vol 12, Academic, New York, pp 445–456

    Google Scholar 

  10. Burn P, Crooks PA, Heatley F et al. (1982) Synthesis and dopaminergic properties of some exoand endo-2-aminobenzonorbornenes designed as rigid analogs of dopamine. J Med Chem 25: 363–368

    Article  PubMed  CAS  Google Scholar 

  11. Burt DR, Enna S, Creese I et al. (1975) Dopamine receptor binding in the corpus striatum of mammalian brain. Proc Natl Acad Sci USA 72: 4655–4659

    Article  PubMed  CAS  Google Scholar 

  12. Cannon JG (1975) Chemistry of dopaminergic agonists. In: Calne DB, Chase TN, Barbeau A (eds) Advances in neurology. Raven, New York, pp 177–183

    Google Scholar 

  13. Cannon JG, Perez Z, Long JP et al. (1979) N-alkyl derivatives of (±)-alphamethyldopamine. J Med Chem 22: 901–907

    Article  PubMed  CAS  Google Scholar 

  14. Casey DL, Digenis GA, Wesner DA et al. (1981) Preparation and preliminary tissue studies of optically active 11C D- and L-phenylalanine. Int J Appl Radiat Isot 32: 325–330

    Article  PubMed  CAS  Google Scholar 

  15. Chaplin ER, Goldberg AL, Diamond I (1976) Leucine oxidation in brain slices and nerve endings. J Neurochem 26: 701–707

    Article  PubMed  CAS  Google Scholar 

  16. Cohen MB, Spolter L, MacDonald NS et al. (1973) Production of 13N-labeled amino acids by enzymatic synthesis. In: New developments in radiopharmaceuticals and labeled compounds. International Atomic Energy Agency, Vienna, vol 1, pp 269–290

    Google Scholar 

  17. Cohen MB, Spolter L, Chang CC et al. (1974) Immobilized enzymes in the production of radio-pharmaceutically pure amino acids labeled with 13N. J Nucl Med 15: 1192–1195

    PubMed  CAS  Google Scholar 

  18. Comar D, Zarifian E, Verhas M et al. (1979) Brain distribution and kinetics of 71C-chlorpromazine in schizophrenics: positron emission tomography studies. Psychiatry Res 1: 23–29

    Article  PubMed  CAS  Google Scholar 

  19. Conway TW, Lansford EM, Shive W (1962) Purification and substrate specificity of a phenylalanine-activating enzyme from Escherichia coli 9723. J Biol Chem 237: 2850–2854

    PubMed  CAS  Google Scholar 

  20. Cools AR (1981) The puzzling cascade of multiple receptors for dopamine. Trends Pharmacol Sci 2: 178–183

    Article  CAS  Google Scholar 

  21. Creese I, Burt DR, Snyder SH (1975) Dopamine receptor binding: differentiation of agonist and antagonist states with [3H]dopamine and [3H]haloperidol. Life Sci 17: 993–1002

    Article  CAS  Google Scholar 

  22. Creese I, Burt DR, Snyder SH (1976) Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science 192: 481–483

    Article  PubMed  CAS  Google Scholar 

  23. Dixon M, Kleppe K ( 1965 a) D-amino acid oxidase. I. dissociation and recombination of the holoenzyme. Biochim Biophys Acta 96: 357–367

    PubMed  CAS  Google Scholar 

  24. Dixon M, Kleppe K (1965b) D-amino acid oxidase. II. specificity, competitive inhibition and reaction sequence. Biochim Biophys Acta 96: 368–382

    CAS  Google Scholar 

  25. Fowler JS, MacGregor RR, Wolf AP et al. (1981) A shielded synthesis system for production of 2deoxy-2-[78F]fluoro-D-glucose. J Nucl Med 22: 376–380

    PubMed  CAS  Google Scholar 

  26. Frost JJ (1982) Pharmacokinetic aspects of the in vivo, noninvasive study of neuroreceptors in man. In: Eckelman WC (ed) Receptor binding radiotracers. CRC Boca Raton, FL, pp. 25–39

    Google Scholar 

  27. Gal EM (1974) Synthetic p-halogenophenylalanines and protein synthesis in the brain. Ciba Found Symp 22: 343–359

    CAS  Google Scholar 

  28. Gallagher BM, Ansari A, Atkins H et al. (1977) Radiopharmaceuticals XXIII. 78F-labeled glucose metabolism in vivo: tissue distribution and imaging studies in animals. J Nucl Med 18: 990–996

    PubMed  CAS  Google Scholar 

  29. Gallagher BM, Fowler JS, Gutterson NI et al. (1978) Metabolic trapping as a principle of radio-pharmaceutical design. The factors responsible for the biodistribution of 78F-2-deoxy-2-fluoro-Dglucose (78FDG). J Nucl Med 19: 1154–1161

    PubMed  CAS  Google Scholar 

  30. Gelbard AS (1981) Biosynthetic methods for incorporating positron-emitting radionuclides into compounds of biomedical interest. J Labelled Compd Radiopharm 18: 933–945

    Article  CAS  Google Scholar 

  31. Gelbard AS, Benua RS, Laughlin JS et al. (1979) Quantitative scanning of osteogenic sarcoma with nitrogen-13-labeled L-glutamate. J Nucl Med 20: 782–784

    PubMed  CAS  Google Scholar 

  32. Gelbard AS, Benua RS, Reiman RE et al. (1980) Imaging of the human heart after administration of L-(73N)glutamate. J Nucl Med 21: 988–991

    PubMed  CAS  Google Scholar 

  33. Gil-Av E, Tishbee A, Hare PE (1980) Resolution of underivatized amino acids by reversed-phase chromatography. J Am Chem Soc 102: 5115–5117

    Article  CAS  Google Scholar 

  34. Giessner-Prettre C, Pullman B (1975) Molecular-orbital study of the orthobenzylic long-range proton-proton coupling constant 41HH in biological phenethylamines. J Magn Reson 18: 564–568

    CAS  Google Scholar 

  35. Goulding RW, Palmer AJ (1972) The preparation of fluorine-18-labeled p-fluorophenylalanine for clinical use. Int J Appl Radiat Isot 23: 133–137

    Article  PubMed  CAS  Google Scholar 

  36. Havekes L, Buckmann F, Visser J (1974) Immobilized glutamate dehydrogenase: some catalytic and structural aspects. Biochim Biophys Acta 334: 272–286

    CAS  Google Scholar 

  37. Henze E, Schelbert HR, Barrio JR et al. (1982) Evaluation of myocardial metabolism with 13N and 11C-labeled amino acids and positron computed tomography. J Nucl Med 23: 671–681

    PubMed  CAS  Google Scholar 

  38. Huang SC, Phelps ME, Hoffman EJ et al. (1980) Noninvasive determination of local cerebral metabolic rate of glucose in man. Am J Physiol 238: E69 - E82

    PubMed  CAS  Google Scholar 

  39. Humber LG, Bruderlein FT, Voith K (1975) Neuroleptic agents of the benzocycloheptapyridoisoquinoline series. A hypothesis on their mode of interaction with the central dopamine receptor. Mol Pharmacol 11: 833–840

    PubMed  CAS  Google Scholar 

  40. Humber LG, Bruderlein FT, Phillip AH et al. ( 1979 a) Mapping the dopamine receptor. I. features derived from modifications in ring E of the neuroleptic butaclamol. J Med Chem 22: 761–767

    Article  PubMed  CAS  Google Scholar 

  41. Humber LG, Phillip AH, Voith K et al. (1979 b) (+) Isobutaclamol: a crystallographic, pharmacological and biochemical study. J Med Chem 22: 899–901

    Google Scholar 

  42. Ido T, Wan CN, Casella V et al. (1978) Labeled 2deoxy-D-glucose analogs. 18F-labeled 2-deoxy-2fluoro-D-glucose, 2-deoxy-2-fluoro-D-mannose and 14C-2-deoxy-2-fluoro-D-glucose. J Labelled Compd Radiopharm 14: 175–183

    Article  CAS  Google Scholar 

  43. Kaufman S (1961) Enzyme conversion of 4-fluorophenylalanine to tyrosine. Biochim Biophys Acta 51: 619–621

    Article  PubMed  CAS  Google Scholar 

  44. Kebabian JW, Caine DB (1979) Multiple receptors for dopamine. Nature 277: 93–96

    Article  PubMed  CAS  Google Scholar 

  45. Kuhar MJ, Murrin LC, Malouf AT et al. (1978) Dopamine receptor binding in vivo: the feasibility of autoradiographic studies. Life Sci 22: 203–210

    Article  PubMed  CAS  Google Scholar 

  46. Laduron P, Leyson J (1977) Specific in vivo binding of neuroleptic drugs in rat brain. Biochem Pharmacol 26: 1003–1007

    Article  PubMed  CAS  Google Scholar 

  47. Laduron PM, Janssen FM, Leyson JE (1978 a) Spiperone: a ligand of choice for neuroleptic receptors. 1. kinetics and characteristics of in vitro binding. Biochem Pharmacol 27: 307–316

    Google Scholar 

  48. Laduron PM, Janssen FM, Leyson JE (1978b) Spiperone: a ligand of choice for neuroleptic receptors 2. regional distribution and in vivo displacement of neuroleptic drugs. Biochem Pharmacol 27: 317–321

    Article  PubMed  CAS  Google Scholar 

  49. Lehninger AL (1975) Biochemistry ( 2nd ed ). Worth, New York

    Google Scholar 

  50. Lund-Anderson H (1979) Transport of glucose from blood to brain. Physiol Rev 59: 305–352

    Google Scholar 

  51. MacGregor RR, Fowler JS, Wolf AP et al. (1981) A synthesis of 2-deoxy-D[1–11C]glucose for regional metabolic studies: concise communication. J Nucl Med 22: 800–803

    PubMed  CAS  Google Scholar 

  52. Murrin LC, Kuhar MJ (1979) Dopamine receptors in the rat frontal cortex: an autoradiographic study. Brain Res 177: 279–285

    Article  PubMed  CAS  Google Scholar 

  53. Niemegeers CJE, Janssen PAJ (1979) A systematic study of the pharmacological activities of dopamine antagonists. Life Sci 24: 2201–2216

    Article  PubMed  CAS  Google Scholar 

  54. Oldendorf WH (1971) Brain uptake of radiolabeled amino acids, amines and hexoses after arterial injection. Am J Physiol 221: 1629–1639

    PubMed  CAS  Google Scholar 

  55. Oldendorf WH, Szabo J (1976) Amino acid as-signment to one of three blood-brain barrier amino acid carriers. Ann J Physiol 230: 94–98

    CAS  Google Scholar 

  56. Padgett HC, Barrio JR, MacDonald NS et al. (1982) The unit operations approach applied to the synthesis of [1_11C12-deoxy-D-glucose for routine clinical applications. J Nucl Med 23: 739–744

    PubMed  Google Scholar 

  57. Palacios JM, Niehoff DL, Kuhar MJ (1981) 3HSpiperone binding sites in brain: Autoradio-graphic localization of multiple receptors. Brain Res 213: 277–289

    Article  PubMed  CAS  Google Scholar 

  58. Phelps ME (1981) Positron computed tomography studies of cerebral glucose metabolism in man: theory and applications in nuclear medicine. Sem in Nucl Med 11: 32–49

    Article  CAS  Google Scholar 

  59. Phelps ME, Hoffman EJ, Kuhl DE (1977) Physiologic tomography: a new approach to in vivo measure of metabolism and physiologic function. In: Medical radionuclide imaging. International Atomic Energy Agency, Vienna, vol 1, pp 233–253

    Google Scholar 

  60. Phelps ME, Huang SC, Hoffmann EJ et al. (1979) Tomographic measurement of local cerebral glucose metabolic rate in humans with 18F 2-fluoro2-deoxy-D-glucose: validation of method. Ann Neurol 6: 371–388

    Article  PubMed  CAS  Google Scholar 

  61. Phelps ME, Kuhl DE, Mazziotta JD (1981) Metabolic mapping of the brain’s response to visual stimulation: Studies in humans. Science 211: 1445–1448

    Article  PubMed  CAS  Google Scholar 

  62. Phelps ME, Barrio JR, Huang S-C et al. (1982) The measurement of local cerebral protein synthesis in man with positron computed tomography ( PCT) and [“C]L-leucine. J Nucl Med 23: 6

    Google Scholar 

  63. Phillip AH, Humber LG, Voith K (1979) Mapping the dopamine receptor. 2. features derived from modifications in the rings A/B region of the neuroleptic butaclamol. J Med Chem 22: 768–773

    Article  Google Scholar 

  64. Pollak A, Blumenfeld H, Wax M et al. (1980) Enzyme immobilization by condensation copolymerization into cross-linked polyacrylamide gels. J Am Chem Soc 102: 6324–6336

    Article  CAS  Google Scholar 

  65. Pullman B, Coubeils JL, Courriere P et al. (1972) Quantum mechanical study of the conformational properties of phenethylamines of biochemical and medicinal interest. J Med Chem 15: 17–23

    Article  PubMed  CAS  Google Scholar 

  66. Quastel JH (1979) The role of amino acids in the brain. Essays Med Biochem 4: 1–48

    CAS  Google Scholar 

  67. Raichle ME, Larson KB, Phelps ME et al. (1975) In vivo measurement of brain glucose transport and metabolism employing [11C] glucose. Am J Physiol 228: 1936–1948

    PubMed  CAS  Google Scholar 

  68. Reivich M, Kuhl D, Wolf A et al. (1979) The [18F]fluorodeoxyglucose method for the measurement of local cerebral glucose utilization in man. Circ Res 44: 127–137

    PubMed  CAS  Google Scholar 

  69. Rekker RF, Engel DJC, Nys GG (1972) Apomorphine and its dopamine-like action. J Pharm Pharmacol 24: 589–591

    Article  PubMed  CAS  Google Scholar 

  70. Schlosser M (1978) Introduction of fluorine into organic molecules: why and how. Tetrahedron 34: 3–17

    Article  CAS  Google Scholar 

  71. Seeman P, Chau-Wong M, Tedesco J et al. (1975) Brain receptors for antipsychotic drugs and dopamine. Direct binding assays. Proc Natl Acad Sci USA 72: 4376–4380

    Article  PubMed  CAS  Google Scholar 

  72. Smith CB, Davidsen L, Deibler G et al. (1980) A method for the determination of local rates of protein synthesis in brain. Trans Am Soc Neurochem 11: 94

    Google Scholar 

  73. Sokoloff L, Reivich M, Kennedy C et al. (1977) The [C-14]deoxy-glucose method for the measurement of local cerebral glucose utilization: theory, procedure and normal values in the conscious and anesthetized albino rat. J Neurochem 28: 897–916

    Article  PubMed  CAS  Google Scholar 

  74. Straatmann MG, Welch MJ (1973) Enzymatic synthesis of 13N-labeled amino acids. Radiat Res 56: 48–56

    Article  PubMed  CAS  Google Scholar 

  75. Tewson TJ, Raichle ME, Welch MJ (1980) Preliminary studies with [78F]haloperidol: A radio-ligand for in vivo studies of the dopamine receptors. Brain Res 192: 291–295

    Article  PubMed  CAS  Google Scholar 

  76. Tosa T, Sato T, Mori T, et al. (1973) Continuous production of L-aspartic by immobilized aspartase. Biotechnol Bioeng 15: 69–84

    Article  CAS  Google Scholar 

  77. Washburn LC, Sun TI’, Byrd BL et al. (1979) High-level production of 11C carboxyl-labeled amino acids. In: Sorenson JA (ed) Radiopharmaceuticals II. Society of Nuclear Medicine, New York, pp 767–777

    Google Scholar 

  78. Washburn LC, Sun TT, Byrd BL et al. (1982) Production of L-[1 71C]valine by HPLC resolution. J Nucl Med 23: 29–33

    PubMed  CAS  Google Scholar 

  79. Williamson JR, Walajtys-Rode E, Coll KE (1979) Effects of branched chain alpha-ketoacids on the metabolism of isolated rat liver cells. J Biol Chem 254: 11511–11520

    PubMed  CAS  Google Scholar 

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Authors
  1. J. R. Barrio
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Editors and Affiliations

  1. Max-Planck-Institut für Neurologische Forschung und Neurologische, Klinik des Krankenhauses Merheim, Ostmerheimer Straße 200, D-5000, Köln 91, Germany

    Wolf-Dieter Heiss

  2. Division of Biophysics, Department of Radiological Sciences and Laboratory of Nuclear Medicine, University of California, 90024, Los Angeles, California, USA

    Michael E. Phelps

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Barrio, J.R. (1983). Biochemical Parameters in Radiopharmaceutical Design. In: Heiss, WD., Phelps, M.E. (eds) Positron Emission Tomography of the Brain. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-95428-3_7

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  • DOI: https://doi.org/10.1007/978-3-642-95428-3_7

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-12130-5

  • Online ISBN: 978-3-642-95428-3

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