Skip to main content

In Vivo Quantitative Whole-Body Perfusion Imaging Using Radiolabeled Copper(II) Bis(Thiosemicarbazone) Complexes and Positron Emission Tomography (PET)

  • Protocol
  • First Online:

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2393))

Abstract

Traditional quantitative perfusion imaging methods require complex data acquisition and analysis strategies; typically require ancillary arterial blood sampling for measurement of input functions; are limited to single organ or tissue regions in an imaging session; and because of their complexity, are not well suited for routine clinical implementation in a standardized fashion that can be readily repeated across diverse clinical sites. The whole-body perfusion method described in this chapter has the advantages of on-demand radiotracer production; simple tissue pharmacokinetics enabling standardized estimation of perfusion; short-lived radionuclides, facilitating repeat or combination imaging procedures; and scalability to support widespread clinical implementation. This method leverages the unique physiological characteristics of radiolabeled copper(II) bis(thiosemicarbazone) complexes and the detection sensitivity of positron emission tomography (PET) to produce quantitatively accurate whole-body perfusion images. This chapter describes the synthesis of ethylglyoxal bis(thosemicarbazonato)copper(II) labeled with copper-62 ([62Cu]Cu-ETS), its unique physiological characteristics, a simple tracer kinetic model for estimation of perfusion using image-derived input functions, and validation of the method against a reference standard perfusion tracer. A detailed description of the methods is provided to facilitate implementation of the perfusion imaging method in PET imaging facilities.

This is a preview of subscription content, log in via an institution.

Buying options

Protocol
USD   49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   219.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   279.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   379.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Springer Nature is developing a new tool to find and evaluate Protocols. Learn more

References

  1. Green MA, Mathias CJ, Welch MJ et al (1990) [62Cu]-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

    CAS  PubMed  Google Scholar 

  2. Shelton ME, Green MA, Mathias CJ et al (1989) Kinetics of copper-PTSM in isolated hearts: a novel tracer for measuring blood flow with positron emission tomography. J Nucl Med 30:1843–1847

    CAS  PubMed  Google Scholar 

  3. Shelton ME, Green MA, Mathias CJ et al (1990) Assessment of regional myocardial and renal blood flow using copper-PTSM and positron emission tomography. Circulation 82:990–997

    Article  CAS  Google Scholar 

  4. Mathias CJ, Green MA, Morrison WB, Knapp DW (1994) Evaluation of Cu-PTSM as a tracer of tumor perfusion: comparison with labeled microspheres in spontaneous canine neoplasms. Nucl Med Biol 21:83–87

    Article  CAS  Google Scholar 

  5. Herrero P, Markham J, Weinheimer CJ et al (1993) Quantification of regional myocardial perfusion with generator-produced 62Cu-PTSM and positron emission tomography. Circulation 87:173–183

    Article  CAS  Google Scholar 

  6. Herrero P, Hartman JJ, Green MA et al (1996) Assessment of regional myocardial perfusion with generator-produced 62Cu-PTSM and PET in human subjects. J Nucl Med 37:1294–1300

    CAS  PubMed  Google Scholar 

  7. Mathias CJ, Welch MJ, Raichle ME et al (1990) 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

    CAS  PubMed  Google Scholar 

  8. Green MA, Mathias CJ, Willis LR et al (2007) Assessment of Cu-ETS as a PET radiopharmaceutical for evaluation of regional renal perfusion. Nucl Med Biol 34:247–255

    Article  CAS  Google Scholar 

  9. Beanlands RS, Muzik O, Mintun MA et al (1992) The kinetics of copper-62-PTSM in the normal human heart. J Nucl Med 33:684–690

    CAS  PubMed  Google Scholar 

  10. Beanlands RS, Muzik O, Hutchins GD et al (1994) Heterogeneity of regional nitrogen-13-labeled ammonia tracer distribution in the normal human heart: comparison with rubidium-82 and copper-62-labeled PTSM. J Nucl Cardiol 1:225–235

    Article  CAS  Google Scholar 

  11. Okazawa H, Yonekura Y, Fujibayashi Y et al (1994) Clinical application and quantitative evaluation of generator-produced copper-62-PTSM as a brain perfusion tracer for PET. J Nucl Med 35:1910–1915

    CAS  PubMed  Google Scholar 

  12. Tadamura E, Tamaki N, Okazawa H et al (1996) Generator-produced copper-62-PTSM as a myocardial PET perfusion tracer compared with nitrogen-13-ammonia. J Nucl Med 37:729–735

    CAS  PubMed  Google Scholar 

  13. Lee KS, Mangner TJ, Petry NA (1991) Evaluation of Cu-62 PTSM in the detection of neural activation foci. J Nucl Med 32(suppl):1072

    Google Scholar 

  14. Okazawa H, Yonekura Y, Fujibayashi Y et al (1996) Measurement of regional cerebral blood flow with copper-62-PTSM and a three-compartment model. J Nucl Med 37:1089–1093

    CAS  PubMed  Google Scholar 

  15. Fujibayashi Y, Wada K, Taniuchi H et al (1993) Mitochondria-selective reduction of 62Cu-pyruvaldehyde bis(N4-methylthiosemicarbazone) (62Cu-PTSM) in the murine brain; a novel radiopharmaceutical for brain positron emission tomography (PET) imaging. Biol Pharm Bull 16:146–149

    Article  CAS  Google Scholar 

  16. Fletcher JW, Logan TF, Eitel JA et al (2015) Whole-body PET/CT evaluation of tumor perfusion using generator-based [62Cu]Cu-ETS: Validation by direct comparison to [15O]water in metastatic renal cell carcinoma. J Nucl Med 56:56–62

    Article  CAS  Google Scholar 

  17. ICRP Publication 23 (1975) Report of the task group on reference man (WS Snyder, chairman). Pergamon Press, Oxford

    Google Scholar 

  18. Leggett RW, Williams LR (1995) A proposed blood circulation model for reference man. Health Phys 69:187–201

    Article  CAS  Google Scholar 

  19. John E, Green MA (1990) Structure-activity relationships for metal-labeled blood flow tracers: comparison of keto aldehyde bis(thiosemicarbazonato)copper(II) derivatives. J Med Chem 33:1764–1770

    Article  CAS  Google Scholar 

  20. Petering HC, Buskirk HH, Underwood GE (1964) The anti-tumor activity of 2-keto-3-ethoxybutyraldehyde bis(thiosemicarbazone) and related compounds. Cancer Res 24:367–372

    CAS  PubMed  Google Scholar 

  21. Mathias CJ, Margenau WH, Brodack JW et al (1991) A remote system for the synthesis of copper-62 labeled Cu(PTSM). Appl Radiat Isot 42:317–320

    Article  CAS  Google Scholar 

  22. Mathias CJ, Bergmann SR, Green MA (1993) Development and validation of a solvent extraction technique for determination of Cu-PTSM in blood. Nucl Med Biol 20:343–349

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from the National Cancer Institute of the National Institutes of Health (CA202695 and CA140299), a National Institutes of Health Short-Term Training Program in Biomedical Sciences Grant (T35 HL110854), and a Radiological Society of North America (RSNA) Research & Education Foundation Research Medical Student Grant Award (Monica Cheng).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gary D. Hutchins .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2022 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Green, M.A., Mathias, C.J., Smith, N.J., Cheng, M., Hutchins, G.D. (2022). In Vivo Quantitative Whole-Body Perfusion Imaging Using Radiolabeled Copper(II) Bis(Thiosemicarbazone) Complexes and Positron Emission Tomography (PET). In: Ossandon, M.R., Baker, H., Rasooly, A. (eds) Biomedical Engineering Technologies. Methods in Molecular Biology, vol 2393. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1803-5_40

Download citation

  • DOI: https://doi.org/10.1007/978-1-0716-1803-5_40

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-1802-8

  • Online ISBN: 978-1-0716-1803-5

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics