Skip to main content
Log in

Advances in PET myocardial perfusion imaging: F-18 labeled tracers

  • Invited review article
  • Published:
Annals of Nuclear Medicine Aims and scope Submit manuscript

Abstract

Coronary artery disease and its related cardiac disorders represent the most common cause of death in the USA and Western world. Despite advancements in treatment and accompanying improvements in outcome with current diagnostic and therapeutic modalities, it is the correct assignment of these diagnostic techniques and treatment options which are crucial. From a diagnostic standpoint, SPECT myocardial perfusion imaging (MPI) using traditional radiotracers like thallium-201 chloride, Tc-99m sestamibi or Tc-99m tetrofosmin is the most utilized imaging technique. However, PET MPI using N-13 ammonia, rubidium-82 chloride or O-15 water is increasing in availability and usage as a result of the growing number of medical centers with new-generation PET/CT systems taking advantage of the superior imaging properties of PET over SPECT. The routine clinical use of PET MPI is still limited, in part because of the short half-life of conventional PET MPI tracers. The disadvantages of these conventional PET tracers include expensive onsite production and inconvenient on-scanner tracer administration making them unsuitable for physical exercise stress imaging. Recently, two F-18 labeled radiotracers with longer radioactive half-lives than conventional PET imaging agents have been introduced. These are flurpiridaz F 18 (formerly known as F-18 BMS747158-02) and F-18 fluorobenzyltriphenylphosphonium. These longer half-life F-18 labeled perfusion tracers can overcome the production and protocol limitations of currently used radiotracers for PET MPI.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Beller GA, Bergmann SR. Myocardial perfusion imaging agents: SPECT and PET. J Nucl Cardiol. 2004;11:71–86.

    Article  PubMed  Google Scholar 

  2. Russell RR, Zaret BL. Nuclear cardiology: present and future. Curr Probl Cardiol. 2006;31:557–629.

    Article  PubMed  Google Scholar 

  3. Klocke FJ, Baird MG, Lorell BH, Bateman TM, Messer JV, Berman DS, O’Gara PT, et al. ACC/AHA/ASNC guidelines for the clinical use of cardiac radionuclide imaging–executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASNC Committee to Revise the 1995 Guidelines for the Clinical Use of Cardiac Radionuclide Imaging). Circulation. 2003;108:1404–18.

    Article  PubMed  Google Scholar 

  4. Higuchi T, Bengel FM. Cardiovascular nuclear imaging: from perfusion to molecular function: non-invasive imaging. Heart. 2008;94:809–16.

    Article  PubMed  Google Scholar 

  5. Bateman TM. Cardiac positron emission tomography and the role of adenosine pharmacologic stress. Am J Cardiol. 2004;94:19–24.

    Article  Google Scholar 

  6. Cecchin D, Zucchetta P, Faggin P, Bolla E, Bui F. 99Mo/99mTc generator shortage: free, Web-based software. J Nucl Med. 2010;51:14–5.

    Google Scholar 

  7. Bateman TM, Heller GV, McGhie AI, Friedman JD, Case JA, Bryngelson JR, et al. Diagnostic accuracy of rest/stress ECG-gated Rb-82 myocardial perfusion PET: comparison with ECG-gated Tc-99m sestamibi SPECT. J Nucl Cardiol. 2006;13:24–33.

    Article  PubMed  Google Scholar 

  8. Bengel FM, Higuchi T, Javadi MS, Lautamaki R. Cardiac positron emission tomography. J Am Coll Cardiol. 2009;54:1–15.

    Article  PubMed  Google Scholar 

  9. Lertsburapa K, Ahlberg AW, Bateman TM, Katten D, Volker L, Cullom SJ, et al. Independent and incremental prognostic value of left ventricular ejection fraction determined by stress gated rubidium 82 PET imaging in patients with known or suspected coronary artery disease. J Nucl Cardiol. 2008;15:745–53.

    PubMed  Google Scholar 

  10. Senthamizhchelvan S, Bravo PE, Esaias C, Lodge MA, Merrill J, Hobbs RF, et al. Human biodistribution and radiation dosimetry of 82Rb. J Nucl Med. 2010;51:1592–9.

    Article  PubMed  Google Scholar 

  11. Lautamaki R, George RT, Kitagawa K, Higuchi T, Merrill J, Voicu C, et al. Rubidium-82 PET-CT for quantitative assessment of myocardial blood flow: validation in a canine model of coronary artery stenosis. Eur J Nucl Med Mol Imaging. 2009;36:576–86.

    Article  PubMed  Google Scholar 

  12. Heller GV, Calnon D, Dorbala S. Recent advances in cardiac PET and PET/CT myocardial perfusion imaging. J Nucl Cardiol. 2009;16:962–9.

    Article  PubMed  Google Scholar 

  13. Yoshida K, Mullani N, Gould KL. Coronary flow and flow reserve by PET simplified for clinical applications using rubidium-82 or nitrogen-13-ammonia. J Nucl Med. 1996;37:1701–12.

    PubMed  CAS  Google Scholar 

  14. Park SJ, Rogers WL, Clinthorne NH. Effects of positron range and annihilation photon acolinearity on image resolution of a Compton PET. IEEE Trans Nucl Sci. 2007;54:1543–52.

    Article  CAS  Google Scholar 

  15. Degli Esposti M. Inhibitors of NADH-ubiquinone reductase: an overview. Biochim Biophys Acta. 1998;1364:222–35.

    Article  PubMed  CAS  Google Scholar 

  16. Yalamanchili P, Wexler E, Hayes M, Yu M, Bozek J, Kagan M, et al. Mechanism of uptake and retention of F-18 BMS-747158–02 in cardiomyocytes: a novel PET myocardial imaging agent. J Nucl Cardiol. 2007;14:782–8.

    Article  PubMed  Google Scholar 

  17. Ravert HT, Madar I, Dannals RF. Radiosynthesis of 3-[F-18]fluoropropyl and 4-[F-18]fluorobenzyl triarylphosphonium ions. J Label Comp Radiopharm. 2004;47:469–76.

    Article  CAS  Google Scholar 

  18. Madar I, Isoda T, Finley P, Angle J, Wahl R. 18F-fluorobenzyl triphenyl phosphonium: a noninvasive sensor of brown adipose tissue thermogenesis. J Nucl Med. 2011;52:808–14.

    Article  PubMed  CAS  Google Scholar 

  19. Yu M, Guaraldi MT, Mistry M, Kagan M, McDonald JL, et al. BMS-747158–02: a novel PET myocardial perfusion imaging agent. J Nucl Cardiol. 2007;14:789–98.

    Article  PubMed  CAS  Google Scholar 

  20. Huisman MC, Higuchi T, Reder S, Nekolla SG, Poethko T, Wester HJ, et al. Initial characterization of an 18F-labeled myocardial perfusion tracer. J Nucl Med. 2008;49:630–6.

    Article  PubMed  Google Scholar 

  21. Muzik O, Beanlands RS, Hutchins GD, Mangner TJ, Nguyen N, Schwaiger M. Validation of nitrogen-13-ammonia tracer kinetic model for quantification of myocardial blood flow using PET. J Nucl Med. 1993;34:83–91.

    PubMed  CAS  Google Scholar 

  22. Leppo JA, Meerdink DJ. Comparison of the myocardial uptake of a technetium-labeled isonitrile analogue and thallium. Circ Res. 1989;65:632–9.

    PubMed  CAS  Google Scholar 

  23. Mullani NA, Goldstein RA, Gould KL, Marani SK, Fisher DJ, O’Brien HA, et al. Myocardial perfusion with rubidium-82. I. Measurement of extraction fraction and flow with external detectors. J Nucl Med. 1983;24:898–906.

    PubMed  CAS  Google Scholar 

  24. Madar I, Ravert HT, Du Y, Hilton J, Volokh L, Dannals RF, et al. Characterization of uptake of the new PET imaging compound 18F-fluorobenzyl triphenyl phosphonium in dog myocardium. J Nucl Med. 2006;47:1359–66.

    PubMed  CAS  Google Scholar 

  25. Madar I, Liu T, O’Rourke B. Novel technique for dynamic PET imaging in isolated perfused hearts. J Nucl Med. 2011;52:333.

    Article  Google Scholar 

  26. Madar I, Ravert H, Dipaula A, Du Y, Dannals RF, Becker L. Assessment of severity of coronary artery stenosis in a canine model using the PET agent 18F-fluorobenzyl triphenyl phosphonium: comparison with 99mTc-tetrofosmin. J Nucl Med. 2007;48:1021–30.

    Article  PubMed  CAS  Google Scholar 

  27. Higuchi T, Nekolla SG, Huisman MM, Reder S, Poethko T, Yu M, et al. A new 18F-labeled myocardial PET tracer: myocardial uptake after permanent and transient coronary occlusion in rats. J Nucl Med. 2008;49:1715–22.

    Article  PubMed  Google Scholar 

  28. Sherif HM, Saraste A, Weidl E, Weber AW, Higuchi T, Reder S, et al. Evaluation of a novel (18)F-labeled positron-emission tomography perfusion tracer for the assessment of myocardial infarct size in rats. Circ Cardiovasc Imaging. 2009;2:77–84.

    Article  PubMed  Google Scholar 

  29. Yu M, Bozek J, Guaraldi M, Kagan M, Azure M, Robinson SP. Cardiac imaging and safety evaluation of BMS747158, a novel PET myocardial perfusion imaging agent, in chronic myocardial compromised rabbits. J Nucl Cardiol. 2010;17:631–6.

    Article  PubMed  Google Scholar 

  30. Sherif HM, Nekolla SG, Saraste A, Reder S, Yu M, Robinson S, et al. Simplified quantification of myocardial flow reserve with flurpiridaz F 18: validation with microspheres in a pig model. J Nucl Med. 2011;52:617–24.

    Article  PubMed  CAS  Google Scholar 

  31. Nekolla SG, Saraste A. Novel F-18-labeled PET myocardial perfusion tracers: bench to bedside. Curr Cardiol Rep. 2011;13:145–50.

    Article  PubMed  Google Scholar 

  32. Higuchi T, Fukushima K, Rischpler C, Isoda T, Javadi MS, Ravert H, et al. Stable delineation of the ischemic area by the PET perfusion tracer 18F-fluorobenzyl triphenyl phosphonium after transient coronary occlusion. J Nucl Med. 2011;52:965–9.

    Article  PubMed  CAS  Google Scholar 

  33. Maddahi J, Berman D, Taillefer R, Udelson J, Devine M, Lazewatsky J, et al. Phase 2 clinical comparison of flurpiridaz F 18 injection PET, SPECT myocardial perfusion imaging for diagnosis of coronary artery disease. J Nucl Med. 2011;52:59.

    Article  Google Scholar 

  34. Maddahi J, Czernin J, Berman D, Taillefer R, Devine M, Lazewatsky J, et al. Comparison of flurpiridaz F 18 PET injection, Tc-99m labeled SPECT myocardial perfusion imaging for identifying severity, extent of stress induced myocardial ischemia in phase 2 clinical trials. J Nucl Med. 2011;52:444.

    Article  Google Scholar 

  35. Rozanski A, Gransar H, Hayes SW, Friedman JD, Hachamovitch R, Berman DS. Comparison of long-term mortality risk following normal exercise vs adenosine myocardial perfusion SPECT. J Nucl Cardiol. 2010;17:999–1008.

    Article  PubMed  Google Scholar 

  36. Chow BJW, Beanlands RS, Lee A, DaSilva JN, deKemp RA, Alkahtani A, et al. Treadmill exercise produces larger perfusion defects than dipyridamole stress N-13 ammonia positron emission tomography. J Am Coll Cardiol. 2006;47:411–6.

    Article  PubMed  Google Scholar 

  37. Levine MG, Ahlberg AW, Mann A, White MP, McGill CC, de Leon CM, et al. Comparison of exercise, dipyridamole, adenosine, and dobutamine stress with the use of Tc-99m tetrofosmin tomographic imaging. J Nucl Cardiol. 1999;6:389–96.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Takahiro Higuchi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rischpler, C., Park, MJ., Fung, G.S.K. et al. Advances in PET myocardial perfusion imaging: F-18 labeled tracers. Ann Nucl Med 26, 1–6 (2012). https://doi.org/10.1007/s12149-011-0552-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12149-011-0552-5

Keywords

Navigation