Skip to main content
Log in

Novel and Simple Carbon-11-Labeled Ammonium Salts as PET Agents for Myocardial Perfusion Imaging

  • Research Article
  • Published:
Molecular Imaging and Biology Aims and scope Submit manuscript

Abstract

Background

Positron emission tomography (PET) has clear advantages over single photon emission computed tomography (SPECT) in the field of myocardial perfusion scintigraphy (MPS); however, there are just a small number of efficient PET tracers available today for MPS. We sought to develop and perform a preliminary biological evaluation of novel carbon-11-labeled ammonium salts as potential MPS PET agents.

Methods and Results

Three potential tracers were labeled and evaluated via biodistribution in mice and PET imaging in both rats and rabbits, and the results obtained were also compared to agents that are routinely used in the clinical practice.

Conclusions

The results designated carbon-11-labeled ammonium salts as having great potential as MPS PET agents. Specifically, carbon-11-labeled trimethyl-phenyl-ammonium iodide ([11C]2) and homologues of higher lipophilicity/charge warrant further studies in larger animals and humans such as measurements of myocardial uptake at rest and stress under both normal and pathological coronary flow conditions.

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.

Scheme 1
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Beller GA (2003) First annual Mario S. Verani, MD, Memorial lecture: clinical value of myocardial perfusion imaging in coronary artery disease. J Nucl Cardiol 10(5):529–542

    Article  PubMed  Google Scholar 

  2. Hachamovitch R, Berman DS, Kiat H et al (2002) Value of stress myocardial perfusion single photon emission computed tomography in patients with normal resting electrocardiograms: an evaluation of incremental prognostic value and cost-effectiveness. Circulation 105(7):823–829

    Article  PubMed  Google Scholar 

  3. Marcassa C, Bax JJ, Bengel F et al (2008) Clinical value, cost-effectiveness, and safety of myocardial perfusion scintigraphy: a position statement. Eur Heart J 29(4):557–563

    Article  PubMed  Google Scholar 

  4. Russell RR 3rd, Zaret BL (2006) Nuclear cardiology: present and future. Curr Probl Cardiol 31(9):557–629

    Article  PubMed  Google Scholar 

  5. Underwood SR, Shaw LJ, Anagnostopoulos C et al (2004) Myocardial perfusion scintigraphy and cost effectiveness of diagnosis and management of coronary heart disease. Heart 90(Suppl 5):v34–v36

    Article  PubMed  Google Scholar 

  6. Rahmim A, Zaidi H (2008) PET versus SPECT: strengths, limitations and challenges. Nuc Med Comm 29(3):193–207

    Article  Google Scholar 

  7. Knaapen P, Lubberink M (2008) Cardiac positron emission tomography: myocardial perfusion and metabolism in clinical practice. Clin Res Cardiol 97(11):791–796

    Article  PubMed  Google Scholar 

  8. Parkash R, deKemp RA, Ruddy TD et al (2004) Potential utility of rubidium 82 PET quantification in patients with 3-vessel coronary artery disease. J Nucl Cardiol 11(4):440–449

    Article  CAS  PubMed  Google Scholar 

  9. Yoshinaga K, Katoh C, Noriyasu K et al (2003) 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 10(3):275–283

    Article  PubMed  Google Scholar 

  10. Aarnoudse WH, Botman KJ, Pijls NH (2003) False-negative myocardial scintigraphy in balanced three-vessel disease, revealed by coronary pressure measurement. Int J Cardiovasc Interv 5(2):67–71

    Google Scholar 

  11. Dahlberg S, Leppo J (2003) Risk stratification of the normal perfusion scan: does normal stress perfusion always mean very low risk? J Nucl Cardiol 10(1):87–91

    Article  PubMed  Google Scholar 

  12. Lima RS, Watson DD, Goode AR et al (2003) Incremental value of combined perfusion and function over perfusion alone by gated SPECT myocardial perfusion imaging for detection of severe three-vessel coronary artery disease. J Am Coll Cardiol 42(1):64–70

    Article  PubMed  Google Scholar 

  13. Ragosta M, Bishop AH, Lipson LC et al (2007) Comparison between angiography and fractional flow reserve versus single-photon emission computed tomographic myocardial perfusion imaging for determining lesion significance in patients with multivessel coronary disease. Am J Cardiol 99(7):896–902

    Article  PubMed  Google Scholar 

  14. Berman DS, Kang X, Slomka PJ et al (2007) Underestimation of extent of ischemia by gated SPECT myocardial perfusion imaging in patients with left main coronary artery disease. J Nucl Cardiol 14(4):521–528

    Article  PubMed  Google Scholar 

  15. Takaro T, Hultgren HN, Lipton MJ, Detre KM (1976) The VA cooperative randomized study of surgery for coronary arterial occlusive disease II. Subgroup with significant left main lesions. Circulation 54(6 Suppl):III107–III117

    CAS  PubMed  Google Scholar 

  16. Travin MI (2007) Is it possible for myocardial perfusion imaging to avoid missing any patients with high-risk coronary disease? J Nucl Cardiol 14(4):492–496

    Article  PubMed  Google Scholar 

  17. Carlin RD, Jan KM (1985) Mechanism of thallium extraction in pump perfused canine hearts. J Nucl Med 26(2):165–169

    CAS  PubMed  Google Scholar 

  18. DePuey EG, Garcia EV, Berman DS (2000) Cardiac SPECT imaging. Lippincott Williams & Wilkins, Philadelphia

    Google Scholar 

  19. Schwaiger M (1994) Myocardial perfusion imaging with PET. J Nucl Med 35(4):693–698

    CAS  PubMed  Google Scholar 

  20. Rauch B, Helus F, Grunze M et al (1985) Kinetics of 13N-ammonia uptake in myocardial single cells indicating potential limitations in its applicability as a marker of myocardial blood flow. Circulation 71(2):387–393

    CAS  PubMed  Google Scholar 

  21. Korsakov MV, Krasikova RN, Fedorova OS (1996) Production of high yield [N-13]ammonia by proton irradiation from pressurized aqueous solutions. J Radioanal Nucl Chem-Artic 204(2):231–239

    Article  CAS  Google Scholar 

  22. van den Hoff J, Burchert W, Borner AR et al (2001) [1-(11)C]Acetate as a quantitative perfusion tracer in myocardial PET. J Nucl Med 42(8):1174–1182

    PubMed  Google Scholar 

  23. Williams G, Kolodny GM (2009) Retrospective study of coronary uptake of 18F-fluorodeoxyglucose in association with calcification and coronary artery disease: a preliminary study. Nuc Med Comm 30(4):287–291

    Article  CAS  Google Scholar 

  24. Huisman MC, Higuchi T, Reder S et al (2008) Initial characterization of an 18F-labeled myocardial perfusion tracer. J Nucl Med 49(4):630–636

    Article  PubMed  Google Scholar 

  25. Yu M, Guaraldi M, Kagan M et al (2009) Assessment of F-18-labeled mitochondrial complex I inhibitors as PET myocardial perfusion imaging agents in rats, rabbits, and primates. Eur J Nucl Med Mol Imaging 36(1):63–72

    Article  CAS  PubMed  Google Scholar 

  26. Madar I, Ravert H, Nelkin B et al (2007) Characterization of membrane potential-dependent uptake of the novel PET tracer 18F-fluorobenzyl triphenylphosphonium cation. Eur J Nucl Med Mol Imaging 34(12):2057–2065

    Article  CAS  PubMed  Google Scholar 

  27. Madar I, Ravert HT, Du Y et al (2006) Characterization of uptake of the new PET imaging compound 18F-fluorobenzyl triphenyl phosphonium in dog myocardium. J Nucl Med 47(8):1359–1366

    CAS  PubMed  Google Scholar 

  28. Marshall RC, Powers-Risius P, Reutter BW et al (2004) Kinetic analysis of 18F-fluorodihydrorotenone as a deposited myocardial flow tracer: comparison to 201Tl. J Nucl Med 45(11):1950–1959

    CAS  PubMed  Google Scholar 

  29. Crouzel C, Långström B, Pike VW, Coenen HH (1987) Recommendations for a practical production of [11C]methyl iodide. Int J Radiat Appl Instrum Appl Radiat Isot 38(8):601–603

    Article  CAS  Google Scholar 

  30. Mishani E, Ben-David I, Rozen Y et al (2001) [C-11] choline-automated preparation and clinical utilization. J Label Compd Radiopharm 44:S379–S381

    Google Scholar 

  31. Kim SW, Yang SD, Ahn BJ et al (2005) In vivo targeting of ERG potassium channels in mice and dogs by a positron-emitting analogue of fluoroclofilium. Exp Mol Med 37(4):269–275

    CAS  PubMed  Google Scholar 

  32. Studenov AR, Berridge MS (2001) Synthesis and properties of 18F-labeled potential myocardial blood flow tracers. Nucl Med Bio 28(6):683–693

    Article  CAS  Google Scholar 

  33. Burns HD, Marzilli LG, Dannals RF et al (1980) 4-[125I] iodophenyltrimethylammonium ion, an iodinated acetylcholinesterase inhibitor with potential as a myocardial imaging agent. J Nucl Med 21(9):875–879

    CAS  PubMed  Google Scholar 

  34. Huang CC, Friedman AM, Rayudu GV, Clark P, Fordham EW (1980) In vivo stability and distribution of [131I]iodomethyl trimethylammonium chloride: concise communication. J Nucl Med 21(7):679–681

    CAS  PubMed  Google Scholar 

  35. Tsubaki H, Nakajima E, Shigehara E, Komai T, Shindo H (1986) The relation between structure and distribution of quaternary ammonium-ions in mince and rats—simple tetraalkylammonium and a series of m-substituted trimethylphenylammonium ions. J Pharmacobio-Dyn 9(9):737–746

    CAS  PubMed  Google Scholar 

  36. Hansch C, Leo A (1987) Log P Database. Pomona College Medicinal Chemistry Project, Claremont, CA 91711

  37. Fowler JS, Gallagher BM, MacGregor RR, Wolf AP (1976) Carbon-11 labeled aliphatic amines in lung uptake and metabolism studies: potential for dynamic measurements in vivo. J Pharmacol Exp Ther 198(1):133–145

    CAS  PubMed  Google Scholar 

  38. Hang LW, Shiau YC, Hsu WH et al (2003) Increased lung uptake of technetium-99m hexamethylpropylene amine oxime in diffuse infiltrative lung disease. Respiration 70(5):479–483

    Article  CAS  PubMed  Google Scholar 

  39. Poulsen LL, Taylor K, Williams DE, Masters BS, Ziegler DM (1986) Substrate specificity of the rabbit lung flavin-containing monooxygenase for amines: oxidation products of primary alkylamines. Mol Pharmacol 30(6):680–685

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Ohad Ilovich’s research was generously supported by the Hoffman Leadership and Responsibility fund, at the Hebrew University.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Eyal Mishani.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ilovich, O., Billauer, H., Dotan, S. et al. Novel and Simple Carbon-11-Labeled Ammonium Salts as PET Agents for Myocardial Perfusion Imaging. Mol Imaging Biol 13, 128–139 (2011). https://doi.org/10.1007/s11307-010-0336-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11307-010-0336-7

Key words

Navigation