Advertisement

62Cu-PTSM: A Generator-Based Radiopharmaceutical for Myocardial Perfusion Imaging

  • Mark A. Green
Part of the Developments in Cardiovascular Medicine book series (DICM, volume 165)

Abstract

Positron emission tomography (PET) is widely recognized as a valuable tool in the study of myocardial physiology and in the clinical diagnosis of cardiac disease. The most commonly used PET radiopharmaceuticals are labeled with cyclotron-produced nuclides, such as 15O, 13N, 11C, and 18F (Table 8-1). For many hospitals, however, the expense of operating a cyclotron for in-house production of these short-lived radionuclides presents a substantial barrier to the clinical use of PET. Positron-emitting isotopes that are instead available from parent/daughter systems potentially offer these hospitals the ability to employ PET while avoiding the initial capital expenditures associated with the purchase and operation of a cyclotron. Thus, generator-produced nuclides, such as 82Rb, 68Ga, and 62Cu, are of interest as potential labels for PET radiotracers [1], despite inherent chemical limitations that generally preclude their use for direct labeling of natural physiological substrates.

Keywords

Positron Emission Tomography Myocardial Perfusion Myocardial Perfusion Image Myocardial Blood Flow Generator Eluate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Green MA. The potential for generator-based PET perfusion tracers. J Nucl Med 31: 1641–1645, 1993.Google Scholar
  2. 2.
    Robinson GD, Zielinski FW, Lee AW. The zinc-62/copper-62 generator: A convenient source of copper-62 radiopharmaceuticals. Int J Appl Radiat Isot 31:111–116, 1980.PubMedCrossRefGoogle Scholar
  3. 3.
    Green MA, Mathias CJ, Welch MJ, Fernandez-Rubio F, Perlmutter JS, Raichle ME, Bergmann SR. Copper-62-labeled pyruvaldehyde bis(N4-methylthiosemicarbazonato) copper(II): Synthesis and evaluation as a positron emission tomography tracer for cerebral and myocardial perfusion. J Nucl Med 31:1989–1996, 1990.PubMedGoogle Scholar
  4. 4.
    Zweit J, Goodall R, Cox M, Babich JW, Potter GA, Sharma HL, Ott RJ. Development of a high performance zinc-62/copper-62 radionuclide generator for positron emission tomography. Eur J Nucl Med 19:418–425, 1992.PubMedCrossRefGoogle Scholar
  5. 5.
    Bormans G, Janssen A, Adriaens P, Crombez D, Witsenboer A, DeGoeij J, Mortelmans L, Verbruggen A. A Zn-62/Cu-62 generator for the routine production of 62Cu-PTSM. Appl Radiat Isot 43:1437–1441, 1992.CrossRefGoogle Scholar
  6. 6.
    Yagi M, Kondo K. A 62Cu generator, Int J Appl Radiat Isot 30:569–570, 1979.CrossRefGoogle Scholar
  7. 7.
    Kraus KA, Moore GE. Anion exchange studies—VI—the divalent transition elements manganese to zinc in hydrochloric acid. J Am Chem Soc 75:1460–1462, 1953.CrossRefGoogle Scholar
  8. 8.
    Mathias CJ, Margenau WH, Brodack JW, Welch MJ, Green MA. A remote system for the synthesis of copper-62 labeled Cu(PTSM). Appl Radiat Isot 42:317–320, 1991.CrossRefGoogle Scholar
  9. 9.
    Green MA, Mathias CJ. Comparison of Zn-62/Cu-62 generators based on Dowex 1 × 8. Abst Pap Am Chem Soc 204, NUCL 0044, 1992.Google Scholar
  10. 10.
    Fujibayashi Y, Matsumoto K, Yonekura Y, Konishi J, Yokoyama A. A new zinc-62/ copper-62 generator as a copper-62 source for PET radiopharmaceuticals. J Nucl Med 30:1838–1842, 1989.PubMedGoogle Scholar
  11. 11.
    John E, Fanwick PE, McKenzie AT, Stowell JG, Green MA. Structural characterization of a metal-based perfusion tracer: Copper(II) pyruvaldehyde bis(N4-methylthiosemicarbazone). Nucl Med Biol 16:791–797, 1989.Google Scholar
  12. 12.
    Green MA. A potential copper radiopharmaceutical for imaging the heart and brain: Copper-labeled pyruvaldehyde bis(N4-methylthiosemicarbazone). Nucl Med Biol 14:59–61, 1987.Google Scholar
  13. 13.
    Green MA, Klippenstein DL, Tennison JR. Copper(II) bis(thiosemicarbazone) complexes as potential tracers for evaluation of cerebral and myocardial blood flow with PET. J Nucl Med 29:1549–1557, 1988.PubMedGoogle Scholar
  14. 14.
    John EK, Green MA. Structure-activity relationships for metal labeled blood flow tracers: Comparison of keto aldehyde bis(thiosemicarbazonato) copper(II) derivatives. J Med Chem 133:1764–1770, 1990.CrossRefGoogle Scholar
  15. 15.
    Mathias GJ, Welch MJ, Raichle ME, Mintun MA, Lieh LL, McGuire AH, Zinn KR, John E, Green MA. Evaluation of a potential generator-produced PET tracer for cerebral perfusion imaging: Single-pass cerebral extraction measurements and imaging with radiolabeled Cu-PTSM. J Nucl Med 31:351–359, 1990.PubMedGoogle Scholar
  16. 16.
    Shelton ME, Green MA, Mathias GJ, Welch MJ, Bergmann SR. Kinetics of copper-PTSM in isolated heart: A novel tracer for measuring blood flow with positron emission tomography. J Nucl Med 30:1843–1847, 1989.PubMedGoogle Scholar
  17. 17.
    Shelton ME, Green MA, Mathias CJ, Welch MJ, Bergmann SR. Assessment of regional myocardial and renal blood flow with copper-PTSM and positron emission tomography. Circulation 82:990–997, 1990.PubMedCrossRefGoogle Scholar
  18. 18.
    Winkelmann DA, Bermke Y, Petering DH. Comparative properties of the antineoplastic agent 3-ethoxy-2-oxobutyraldehyde bis(thiosemicarbazone) copper(II) and related chelates: Linear free energy relationships. Bioinorg. Chem 3:261–277, 1974.Google Scholar
  19. 19.
    Petering DH. Carcinostatic copper complexes. In: Sigel H (ed): Metal Ions in Biological Systems. New York: Marcel Dekker 1980, pp 197–229.Google Scholar
  20. 20.
    Minkel DT, Saryan LA, Petering DH. Structure-function correlations in the reaction of bis(thiosemicarbazone) copper(II) complexes with Ehrlich acites tumor cells. Cancer Res 38:124–129, 1978.PubMedGoogle Scholar
  21. 21.
    Meister A, Anderson ME. Glutathione. Annu Rev Biochem 52:711–760, 1983.PubMedCrossRefGoogle Scholar
  22. 22.
    Kostyniak PJ, Maccubbin AE, Nakeeb SM, John EK, Green MA, Schopp EM, Kung HF. Acute toxicity and mutagenicity of the copper complex of pyruvaldehyde bis(N4-methylthiosemicarbazone), Cu-PTSM. J Appl Toxicol 10:417–421, 1990.PubMedCrossRefGoogle Scholar
  23. 23.
    Green MA. Myocardial perfusion imaging with copper-62 labeled Cu-PTSM. In: van der Wall EE, Sochor H, Righetti A, Niemeyer MG (eds): What’s New in Cardiac Imaging? Dordrecht: Kluwer, 1992, pp 165–177.CrossRefGoogle Scholar
  24. 24.
    Regelson W, Holland JF, Talley RW. Clinical pharmacologic study of ethoxal bis(thiosemicarbazone) [NSC-82116] in advanced cancer. Cancer Chemother Rep 51:171–177, 1967.PubMedGoogle Scholar
  25. 25.
    Petering HG, Buskirk HH, Underwood GE. The anti-tumor activity of 2-keto-3-ethoxybutyraldehyde bis(thiosemicarbazone) and related compounds. Cancer Res 24:367–372, 1964.PubMedGoogle Scholar
  26. 26.
    Mathias CJ, Welch MJ, Green MA, Diril H, Meares CF, Gropler RJ, Bergmann SR. In vivo comparison of copper blood-pool agents: Potential radiopharmaceuticals for use with copper-62. J Nucl Med 32:475–480, 1991.PubMedGoogle Scholar
  27. 27.
    Herrero P, Markham J, Weinheimer CJ, Anderson CJ, Welch MJ, Green MA, Bergmann SR. Quantification of regional myocardial perfusion with generator produced 62Cu-PTSM and positron emission tomography. Circulation 87:173–183, 1993.PubMedGoogle Scholar
  28. 28.
    Herrero P, Markham J, Weinheimer J, Green MA, Welch MJ, Bergmann SR. Quantification of myocardial perfusion with Cu-62 PTSM and positron emission tomography. J Nucl Med 32:937, 1991.Google Scholar
  29. 29.
    Bergmann SR, Herrero P, Anderson CJ, Welch MJ, Green MA. Measurement of regional myocardial perfusion in human subjects using copper-62-PTSM. J Nucl Med 33:837, 1992.Google Scholar
  30. 30.
    Beanlands R, Muzik O, Lee K, Mintun MA, Mangner T, Moskwa J, Hutchins, G, Allman K, Petry N, Nguyen N, Schwaiger M. Evaluation of copper-62 PTSM as a myocardial flow tracer. J Nucl Med 32:1028, 1991.Google Scholar
  31. 31.
    Benlands RSB, Muzik O, Mintun M, Mangner T, Lee K, Petry N, Hutchins GD, Schwaiger M. The kinetics of copper-62-PTSM in the normal human heart. J Nucl Med 33:684–690, 1992.Google Scholar
  32. 32.
    Mathias CJ, Bergmann SR, Green MA. Development and validation of a solvent extraction technique for determination of Cu-PTSM in blood. Nucl Med Biol 20:343–349, 1993.PubMedCrossRefGoogle Scholar
  33. 33.
    Stone CK, Martin CC, Mueller B, Pyzalski RA, Perlman SB, Nickles RJ. Comparison of myocardial uptake of copper pyruvaldehyde thiosemicarbazone with N-13 ammonia in humans by PET. J Nucl Med 32:999, 1991.Google Scholar
  34. 34.
    Martin CC, Oakes TR, Nickles RJ. Small cyclotron production of [Cu-60] Cu-PTSM for PET blood flow measurements. J Nucl Med 31:815, 1990.Google Scholar
  35. 35.
    Mathias CJ, Bergmann SR, Green MA. Species-dependent binding of copper (II) Bis (thiosemicarbazone) radiopharmaceuticals to serum albumin. J Nucl Med 36: in press, 1995.Google Scholar

Copyright information

© Kluwer Academic Publishers 1996

Authors and Affiliations

  • Mark A. Green

There are no affiliations available

Personalised recommendations