Skip to main content

Advertisement

SpringerLink
Log in

Quantitative analysis of coronary endothelial function with generator-produced 82Rb PET: comparison with 15O-labelled water PET

  • Original Article
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Endothelial dysfunction is the earliest abnormality in the development of coronary atherosclerosis. 82Rb is a generator-produced positron emission tomography (PET) myocardial perfusion tracer that is becoming more widely used. We aimed to (1) develop a method for quantitative assessment of coronary endothelial function using the myocardial blood flow (MBF) response during a cold pressor test (CPT) in smokers, measured using 82Rb PET, and (2) compare the results with those measured using 15O-water PET.

Methods

MBF was assessed at rest and during the CPT with 82Rb and 15O-water in nine controls and ten smokers. A one-compartment model with tracer extraction correction was used to estimate MBF with both tracers. CPT response was calculated as the ratio of MBF during the CPT to MBF at rest.

Results

At rest, measurements of MBF for smokers vs controls were not different using 15O-water (0.86 ± 0.18 vs 0.70 ± 0.13, p = 0.426) than they were using 82Rb (0.83 ± 0.23 vs 0.62 ± 0.20, p = 0.051). Both methods showed a reduced CPT response in smokers vs controls (15O-water, 1.03 ± 0.21 vs 1.42 ± 0.29, p = 0.006; 82Rb, 1.02 ± 0.28 vs 1.70 ± 0.52, p < 0.001). There was high reliability [intraclass correlation coefficients: 0.48 (0.07, 0.75)] of MBF measurement between 82Rb and 15O-water during the CPT.

Conclusion

Using a CPT, 82Rb MBF measurements detected coronary endothelial dysfunctions in smokers. 82Rb MBF measurements were comparable to those made using the 15O-water approach. Thus, 82Rb PET may be applicable for risk assessments or evaluation of risk factor modification in subjects with coronary risk factors.

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

Access this article

Log in via an institution

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

Similar content being viewed by others

References

  1. Verma S, Anderson TJ. Fundamentals of endothelial function for the clinical cardiologist. Circulation 2002;105:546–9.

    Article  CAS  PubMed  Google Scholar 

  2. Lerman A, Zeiher AM. Endothelial function: cardiac events. Circulation 2005;111:363–8.

    Article  PubMed  Google Scholar 

  3. Campisi R, Czernin J, Schöder H, Sayre JW, Marengo FD, Phelps ME, et al. Effects of long-term smoking on myocardial blood flow, coronary vasomotion, and vasodilator capacity. Circulation 1998;98:119–25.

    CAS  PubMed  Google Scholar 

  4. Naya M, Tsukamoto T, Morita K, Katoh C, Furumoto T, Fujii S, et al. Olmesartan, but not amlodipine, improves endothelium-dependent coronary dilation in hypertensive patients. J Am Coll Cardiol 2007;50:1144–9.

    Article  CAS  PubMed  Google Scholar 

  5. Prior JO, Schindler TH, Facta AD, Hernandez-Pampaloni M, Campisi R, Dahlbom M, et al. Determinants of myocardial blood flow response to cold pressor testing and pharmacologic vasodilation in healthy humans. Eur J Nucl Med Mol Imaging 2007;34:20–7.

    Article  PubMed  Google Scholar 

  6. Schindler TH, Nitzsche EU, Schelbert HR, Olschewski M, Sayre J, Mix M, et al. Positron emission tomography-measured abnormal responses of myocardial blood flow to sympathetic stimulation are associated with the risk of developing cardiovascular events. J Am Coll Cardiol 2005;45:1505–12.

    Article  PubMed  Google Scholar 

  7. Ezzati M, Henley SJ, Thun MJ, Lopez AD. Role of smoking in global and regional cardiovascular mortality. Circulation 2005;112:489–97.

    Article  PubMed  Google Scholar 

  8. Zeiher AM, Drexler H, Wollschläger H, Just H. Endothelial dysfunction of the coronary microvasculature is associated with coronary blood flow regulation in patients with early atherosclerosis. Circulation 1991;84:1984–92.

    CAS  PubMed  Google Scholar 

  9. Celermajer DS. Reliable endothelial function testing: at our fingertips? Circulation 2008;117:2428–30.

    Article  PubMed  Google Scholar 

  10. Knuuti J, Bengel FM. Positron emission tomography and molecular imaging. Heart 2008;94:360–7.

    Article  CAS  PubMed  Google Scholar 

  11. Bengel FM, Abletshauser C, Neverve J, Schnell O, Nekolla SG, Standl E, et al. Effects of nateglinide on myocardial microvascular reactivity in type 2 diabetes mellitus—a randomized study using positron emission tomography. Diabet Med 2005;22:158–63.

    Article  CAS  PubMed  Google Scholar 

  12. Di Carli MF, Tobes MC, Mangner T, Levine AB, Muzik O, Chakroborty P, et al. Effects of cardiac sympathetic innervation on coronary blood flow. N Engl J Med 1997;336:1208–15.

    Article  PubMed  Google Scholar 

  13. Iwado Y, Yoshinaga K, Furuyama H, Ito Y, Noriyasu K, Katoh C, et al. Decreased endothelium-dependent coronary vasomotion in healthy young smokers. Eur J Nucl Med Mol Imaging 2002;29:984–90.

    Article  CAS  PubMed  Google Scholar 

  14. Camici PG, Crea F. Coronary microvascular dysfunction. N Engl J Med 2007;356:830–40.

    Article  CAS  PubMed  Google Scholar 

  15. Yoshinaga K, Chow BJ, dekemp RA, Thorn S, Ruddy TD, Davies RA, et al. Application of cardiac molecular imaging using positron emission tomography in evaluation of drug and therapeutics for cardiovascular disorders. Curr Pharm Des 2005;11:903–32.

    Article  CAS  PubMed  Google Scholar 

  16. 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 

  17. 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 

  18. Yoshinaga K, Chow BJ, Williams K, Chen L, deKemp RA, Garrard L, et al. What is the prognostic value of myocardial perfusion imaging using rubidium-82 positron emission tomography? J Am Coll Cardiol 2006;48:1029–39.

    Article  PubMed  Google Scholar 

  19. El Fakhri G, Kardan A, Sitek A, Dorbala S, Abi-Hatem N, Lahoud Y, et al. Reproducibility and accuracy of quantitative myocardial blood flow assessment with (82)Rb PET: comparison with (13)N-ammonia PET. J Nucl Med 2009;50:1062–71.

    Article  PubMed  Google Scholar 

  20. Herrero P, Markham J, Shelton ME, Bergmann SR. Implementation and evaluation of a two-compartment model for quantification of myocardial perfusion with rubidium-82 and positron emission tomography. Circ Res 1992;70:496–507.

    CAS  PubMed  Google Scholar 

  21. Lortie M, Beanlands RS, Yoshinaga K, Klein R, Dasilva JN, DeKemp RA. Quantification of myocardial blood flow with 82Rb dynamic PET imaging. Eur J Nucl Med Mol Imaging 2007;34:1765–74.

    Article  PubMed  Google Scholar 

  22. Manabe O, Yoshinaga K, Katoh C, Naya M, deKemp RA, Tamaki N. Repeatability of rest and hyperemic myocardial blood flow measurements with 82Rb dynamic PET. J Nucl Med 2009;50:68–71.

    Article  PubMed  Google Scholar 

  23. 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.

    CAS  PubMed  Google Scholar 

  24. Diamond GA, Forrester JS. Analysis of probability as an aid in the clinical diagnosis of coronary-artery disease. N Engl J Med 1979;300:1350–8.

    Article  CAS  PubMed  Google Scholar 

  25. Siegrist PT, Gaemperli O, Koepfli P, Schepis T, Namdar M, Valenta I, et al. Repeatability of cold pressor test-induced flow increase assessed with H(2)(15)O and PET. J Nucl Med 2006;47:1420–6.

    PubMed  Google Scholar 

  26. Yoshinaga K, Katoh C, Noriyasu K, Iwado Y, Furuyama H, Ito Y, et al. Reduction of coronary flow reserve in areas with and without ischemia on stress perfusion imaging in patients with coronary artery disease: a study using oxygen 15-labeled water PET. J Nucl Cardiol 2003;10:275–83.

    Article  PubMed  Google Scholar 

  27. Furuyama H, Odagawa Y, Katoh C, Iwado Y, Yoshinaga K, Ito Y, et al. Assessment of coronary function in children with a history of Kawasaki disease using (15)O-water positron emission tomography. Circulation 2002;105:2878–84.

    Article  PubMed  Google Scholar 

  28. Katoh C, Morita K, Shiga T, Kubo N, Nakada K, Tamaki N. Improvement of algorithm for quantification of regional myocardial blood flow using 15O-water with PET. J Nucl Med 2004;45:1908–16.

    PubMed  Google Scholar 

  29. Shrout P, Fleiss JL. Intraclass correlation: uses in assessing rater reliability. Psychol Bull 1979;86:420–8.

    Article  CAS  PubMed  Google Scholar 

  30. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986;1:307–10.

    CAS  PubMed  Google Scholar 

  31. Cohen J. A power primer. Psychol Bull 1992;112:155–9.

    Article  CAS  PubMed  Google Scholar 

  32. Schroeder SA. Tobacco control in the wake of the 1998 master settlement agreement. N Engl J Med 2004;350:293–301.

    Article  CAS  PubMed  Google Scholar 

  33. Bergmann SR, Fox KA, Rand AL, McElvany KD, Welch MJ, Markham J, et al. Quantification of regional myocardial blood flow in vivo with H215O. Circulation 1984;70:724–33.

    CAS  PubMed  Google Scholar 

  34. Prior JO, Quiñones MJ, Hernandez-Pampaloni M, Facta AD, Schindler TH, Sayre JW, et al. Coronary circulatory dysfunction in insulin resistance, impaired glucose tolerance, and type 2 diabetes mellitus. Circulation 2005;111:2291–8.

    Article  CAS  PubMed  Google Scholar 

  35. Kaufmann PA, Gnecchi-Ruscone T, di Terlizzi M, Schäfers KP, Lüscher TF, Camici PG. Coronary heart disease in smokers: vitamin C restores coronary microcirculatory function. Circulation 2000;102:1233–8.

    CAS  PubMed  Google Scholar 

  36. Positron emission tomography. In: Cherry S, Sorenson, J, Phelps, M, editors. Physics in nuclear medicine. Philadelphia: Saunders; 2003. p. 325–59.

  37. Lautamäki 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 

  38. Machac J, Bacharach SL, Bateman TM, Bax JJ, Beanlands R, Bengel F, et al. Positron emission tomography myocardial perfusion and glucose metabolism imaging. J Nucl Cardiol 2006;13:e121–51.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank Sayaka Takamori, RT, Keiichi Magota, RT, Hiroshi Arai, RT, Hidehiko Omote, RT, Kyotaro Suzuma, MS, and Ken-ichi Nishijima, Ph.D., for their technical expertise and Eriko Suzuki for her administrative support of this study. This study was supported in part by grants from the Ministry of Education, Science and Culture (No.19591395) and Northern Advancement Center for Science & Technology (Sapporo, Japan) (Grant #H19-C-068). Ran Klein was supported by the JSPS and NSERC Summer Program (2008) (Tokyo, Japan and Ottawa, Ontario, Canada). Rob S.B. Beanlands is a Career Investigator supported by the Heart and Stroke Foundation of Ontario.

Author information

Authors and Affiliations

  1. Department of Photobiology, Division of Molecular/Cellular Imaging, Hokkaido University Graduate School of Medicine, Kita 15 Nishi 7, Kita-Ku, Sapporo, Hokkaido, Japan, 060-8638

    Keiichiro Yoshinaga

  2. Department of Nuclear Medicine, Hokkaido University of Graduate School of Medicine, Sapporo, Japan

    Osamu Manabe, Ran Klein & Nagara Tamaki

  3. Department of Health Sciences, Hokkaido University of Graduate School of Medicine, Sapporo, Japan

    Chietsugu Katoh

  4. Department of Cardiology, Hokkaido University of Graduate School of Medicine, Sapporo, Japan

    Masanao Naya

  5. National Cardiac PET Centre, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada

    Li Chen, Ran Klein, Robert A. deKemp, Kathryn Williams & Rob S. B. Beanlands

Authors
  1. Keiichiro Yoshinaga
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Osamu Manabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chietsugu Katoh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Li Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ran Klein
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Masanao Naya
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Robert A. deKemp
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kathryn Williams
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Rob S. B. Beanlands
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Nagara Tamaki
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Keiichiro Yoshinaga.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yoshinaga, K., Manabe, O., Katoh, C. et al. Quantitative analysis of coronary endothelial function with generator-produced 82Rb PET: comparison with 15O-labelled water PET. Eur J Nucl Med Mol Imaging 37, 2233–2241 (2010). https://doi.org/10.1007/s00259-010-1541-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-010-1541-y

Keywords

Search

Navigation