Journal of Nuclear Cardiology

, Volume 13, Issue 6, pp 779–790 | Cite as

Organ biodistribution and myocardial uptake, washout, and redistribution kinetics of Tc-99m N-DBODC5 when injected during vasodilator stress in canine models of coronary stenoses

  • Kengo Hatada
  • Mirta Ruiz
  • Laurent M. Riou
  • Ronaldo L. Lima
  • Allen R. Goode
  • Denny D. Watson
  • George A. Beller
  • David K. Glover
Article

Abstract

Background

Technetium 99m N-DBODC5 is a new myocardial perfusion tracer shown to exhibit high heart uptake and rapid liver clearance in normal rats. The objectives of this canine study were (1) to compare the organ biodistribution and myocardial uptake, washout, and redistribution kinetics of Tc-99m N-DBODC5 with Tc-99m sestamibi over a period of 3 hours in a more clinically relevant large animal species and (2) to compare the myocardial uptake of Tc-99m N-DBODC5 with thallium 201 when co-injected during vasodilator stress in dogs with coronary stenoses.

Methods and Results

At peak adenosine-induced hyperemia, 10 dogs with critical left anterior descending artery stenoses received either Tc-99m N-DBODC5 (n = 6) or Tc-99m sestamibi (n = 4) and microspheres, followed by serial imaging and blood sampling over a period of 3 hours. Another 14 dogs with either critical (n = 7) or mild (n = 7) left anterior descending artery stenoses underwent simultaneous injection of Tc-99m N-DBODC5, Tl-201, and microspheres during peak vasodilator stress. Like sestamibi, Tc-99m NDBODC5 showed good myocardial uptake with slow washout and minimal redistribution over a period of 3 hours (P = not significant); however, Tc-99m N-DBODC5 cleared more rapidly from the liver (heart-lung ratio at 30 minutes, 0.92 ± 0.11 versus 0.51 ± 0.05; P < .05). When injected during hyperemic flow, the myocardial extraction plateau for Tc-99m NDBODC5 was lower than that for Tl-201 and was intermediate between Tc-99m sestamibi and Tc-99m tetrofosmin.

Conclusions

Excellent organ biodistribution and myocardial uptake and clearance kinetic properties, combined with rapid liver clearance and a favorable flow-extraction relationship, make Tc-99m N-DBODC5 a very promising new myocardial perfusion imaging agent.

Key Words

Radioisotopes technetium biodistribution liver clearance extraction redistribution 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Boschi A, Bolzati C, Uccelli L, et al. A class of asymmetrical nitrido 99mTc heterocomplexes as heart imaging agents with improved biological properties. Nucl Med Commun 2002;23:689–933.PubMedCrossRefGoogle Scholar
  2. 2.
    Boschi A, Uccelli L, Bolzati C, et al. Synthesis and biologic evaluation of monocationic asymmetric 99mTc-nitride heterocomplexes showing high heart uptake and improved imaging properties. J Nucl Med 2003;44:806–14.PubMedGoogle Scholar
  3. 3.
    Hatada K, Riou LM, Ruiz M, et al. 99mTc-N-DBODC5, a new myocardial perfusion imaging agent with rapid liver clearance: comparison with 99mTc-sestamibi and 99mTc-tetrofosmin in rats. J Nucl Med 2004;45:2095–101.PubMedGoogle Scholar
  4. 4.
    Wackers FJ, Berman DS, Maddahi J, et al. Technetium-99m hexakis 2-methoxyisobutyl isonitrile: human biodistribution, dosimetry, safety, and preliminary comparison to thallium-201 for myocardial perfusion imaging. J Nucl Med 1989;30:301–11.PubMedGoogle Scholar
  5. 5.
    Higley B, Smith FW, Smith T, et al. Technetium-99m-1,2- bis[bis(2-ethoxyethyl) phosphino]ethane: human biodistribution, dosimetry and safety of a new myocardial perfusion imaging agent. J Nucl Med 1993;34:30–8.PubMedGoogle Scholar
  6. 6.
    Jain D, Wackers FJ, Mattera J, McMahon M, Sinusas AJ, Zaret BL. Biokinetics of technetium-99m-tetrofosmin: myocardial perfusion imaging agent: implications for a one-day imaging protocol. J Nucl Med 1993;34:1254–9.PubMedGoogle Scholar
  7. 7.
    O’Connor MK, Kelly BJ. Evaluation of techniques for the elimination of “hot” bladder artifacts in SPECT of the pelvis. J Nucl Med 1990;31:1872–5.PubMedGoogle Scholar
  8. 8.
    Chua T, Kiat H, Germano G, et al. Rapid back to back adenosine stress/rest technetium-99m teboroxime myocardial perfusion SPECT using a triple-detector camera. J Nucl Med 1993;34:1485–93.PubMedGoogle Scholar
  9. 9.
    Germano G, Chua T, Kiat H, Areeda JS, Berman DS. A quantitative phantom analysis of artifacts due to hepatic activity in technetium-99m myocardial perfusion SPECT studies. J Nucl Med 1994;35:356–9.PubMedGoogle Scholar
  10. 10.
    Nuyts J, Dupont P, Van den Maegdenbergh V, Vleugels S, Suetens P, Mortelmans L. A study of the liver-heart artifact in emission tomography. J Nucl Med 1995;36:133–9.PubMedGoogle Scholar
  11. 11.
    Matsunari I, Tanishima Y, Taki J, et al. Early and delayed technetium-99m-tetrofosmin myocardial SPECT compared in normal volunteers. J Nucl Med 1996;37:1622–6.PubMedGoogle Scholar
  12. 12.
    Kailasnath P, Sinusas AJ. Comparison of Tl-201 with Tc-99m- labeled myocardial perfusion agents: technical, physiologic, and clinical issues. J Nucl Cardiol 2001;8:482–98.PubMedCrossRefGoogle Scholar
  13. 13.
    Moore CA, Cannon J, Watson DD, Kaul S, Beller GA. Thallium 201 kinetics in stunned myocardium characterized by severe postischemic systolic dysfunction. Circulation 1990;81:1622–32.PubMedGoogle Scholar
  14. 14.
    Glover DK, Ruiz M, Yang JY, Smith WH, Watson DD, Beller GA.Myocardial 99mTc-tetrofosmin uptake during adenosine-induced vasodilatation with either a critical or mild coronary stenosis: comparison with 201Tl and regional myocardial blood flow. Circulation 1997;96:2332–8.PubMedGoogle Scholar
  15. 15.
    Glover DK, Ruiz M, Takehana K, et al. Pharmacological stress myocardial perfusion imaging with the potent and selective A(2A) adenosine receptor agonists ATL193 and ATL146e administered by either intravenous infusion or bolus injection. Circulation 2001;104:1181–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Glover DK, Ruiz M, Edwards NC, et al. Comparison between 201Tl and 99mTc sestamibi uptake during adenosine-induced vasodilation as a function of coronary stenosis severity. Circulation 1995;91:813–20.PubMedGoogle Scholar
  17. 17.
    Smith WH, Watson DD. Technical aspects of myocardial planar imaging with technetium-99m sestamibi. Am J Cardiol 1990;66:16E-22E.PubMedCrossRefGoogle Scholar
  18. 18.
    Sinusas AJ, Beller GA, Smith WH, Vinson EL, Brookeman V, Watson DD. Quantitative planar imaging with technetium-99m methoxyisobutyl isonitrile: comparison of uptake patterns with thallium-201. J Nucl Med 1989;30:1456–63.PubMedGoogle Scholar
  19. 19.
    Heymann MA, Payne BD, Hoffman JI, Rudolph AM. Blood flow measurements with radionuclide-labeled particles. Prog Cardiovasc Dis 1977;20:55–79.PubMedCrossRefGoogle Scholar
  20. 20.
    Jain D. Technetium-99m labeled myocardial perfusion imaging agents. Semin Nucl Med 1999;29:221–36.PubMedCrossRefGoogle Scholar
  21. 21.
    Okada RD, Glover D, Gaffney T, Williams S. Myocardial kinetics of technetium-99m-hexakis-2-methoxy-2-methylpropyl-isonitrile. Circulation 1988;77:491–8.PubMedGoogle Scholar
  22. 22.
    Kelly JD, Forster AM, Higley B, et al. Technetium-99mtetrofosmin as a new radiopharmaceutical for myocardial perfusion imaging. J Nucl Med 1993;34:222–7.PubMedGoogle Scholar
  23. 23.
    Nakajima K, Taki J, Shuke N, Bunko H, Takata S, Hisada K. Myocardial perfusion imaging and dynamic analysis with technetium- 99m tetrofosmin. J Nucl Med 1993;34:1478–84.PubMedGoogle Scholar
  24. 24.
    Schwaiger M, Melin J. Cardiological applications of nuclear medicine. Lancet 1999;354:661–6.PubMedCrossRefGoogle Scholar
  25. 25.
    Sansoy V, Glover DK, Watson DD, et al. Comparison of thallium- 201 resting redistribution with technetium-99m-sestamibi uptake and functional response to dobutamine for assessment of myocardial viability. Circulation 1995;92:994–1004.PubMedGoogle Scholar
  26. 26.
    Glover DK, Okada RD. Myocardial technetium 99m sestamibi kinetics after reperfusion in a canine model. Am Heart J 1993;125:657–666.PubMedCrossRefGoogle Scholar
  27. 27.
    Mousa SA, Cooney JM, Williams SJ. Relationship between regional myocardial blood flow and the distribution of 99mTcsestamibi in the presence of total coronary artery occlusion. Am Heart J 1990;119:842–7.PubMedCrossRefGoogle Scholar
  28. 28.
    Gosselin RE, Stibitz GR. Rates of solute absorption from tissue depots: theoretical considerations. Pflugers Arch 1970;318:85–98.PubMedCrossRefGoogle Scholar

Copyright information

© American Society of Nuclear Cardiology 2006

Authors and Affiliations

  • Kengo Hatada
    • 1
  • Mirta Ruiz
    • 2
  • Laurent M. Riou
    • 3
  • Ronaldo L. Lima
    • 4
  • Allen R. Goode
    • 2
  • Denny D. Watson
    • 2
  • George A. Beller
    • 2
  • David K. Glover
    • 2
  1. 1.Second Department of Internal Medicine, Cardiovascular DivisionKansai Medical University Takii Hospital Moriguchi CityOsakaJapan
  2. 2.Experimental Nuclear Cardiology Laboratory, Cardiovascular Division, Department of MedicineUniversity of Virginia Health SystemCharlottesville
  3. 3.INSERM E 0340 Radiopharmaceutiques Biocliniques Faculté de Médicine de GrenobleDomaine de la MerciLa TroncheFrance
  4. 4.Hospital Universitario Clementino Fraga FilhoUniversidade Federal do Rio de Janeiro, and Faculdade de Medicina da Universidade Estacio de SaRio de JaneiroBrazil

Personalised recommendations