Abstract
Purpose
123I-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (123I-BMIPP) is a fatty acid analog for single-photon emission computed tomography (SPECT) imaging that is mainly stored in the triglyceride pool. Low-dose dobutamine infusion has been reported to improve BMIPP uptake in the stunned myocardium, but the mechanism underlying this effect remains unclear. The purpose of this study was therefore to investigate the myocardial metabolism of 123I-BMIPP in the stunned myocardium under low-dose dobutamine infusion, and to elucidate the mechanism by which dobutamine improves BMIPP uptake.
Methods
Using open-chest dogs, stunned myocardium was induced by occlusion of the left anterior descending artery (LAD) for 30 min, with subsequent reperfusion (ischemia group, n=6). After direct injection of BMIPP into the LAD, myocardial extraction and retention were examined and metabolites evaluated (using high-performance liquid chromatography) during dobutamine infusion. The results in the ischemia group were compared with findings obtained in a control group under dobutamine infusion (n=6).
Results
Dobutamine infusion significantly increased both the rapid extraction (within 30 s) of BMIPP into the myocardium (control vs ischemia group: 48±19% vs 66±14%, p<0.05) and its subsequent retention (73±13% vs 85±8%, p<0.05). The metabolites from the myocardium consisted of back diffusion of nonmetabolized BMIPP, the alpha-oxidation metabolite, intermediate metabolites, and the full-oxidation metabolite. Among these metabolites, the full-oxidation metabolite decreased significantly (from 34.0±20.0% to 15.8±9.3%, p<0.05) in the stunned regions, though back diffusion of nonmetabolized BMIPP increased (from 51.3±21.9% to 71.3±10.1%, p<0.05).
Conclusion
These results indicate that increased uptake of BMIPP in stunned myocardium is mainly due to decreased beta-oxidation in tissue and increased shunt retention of BMIPP in the triglyceride pool, and thereby provide further insight into the pathophysiology of stunned myocardium.
Similar content being viewed by others
References
Knapp FF Jr, Kropp J. Iodine-123-labeled fatty acids for myocardial SPECT: current status and future perspectives. Eur J Nucl Med 1995;22:361•81.
Knapp FF Jr, Kropp J, Goodman MM, et al. The development of iodine-123-methyl-branched fatty acids and their applications in nuclear cardiology. Ann Nucl Med 1993;7:1•14.
Knapp FF Jr, Goodman MM, Ambrose KR, et al. The development of radioiodinated 3-methyl-branched fatty acids for evaluation of myocardial disease by single photon techniques. In: van der Wall EE, editor. Noninvasive imaging of cardiac metabolism. Dordrecht: Martius Nijhoff; 1987. p. 159•201.
Fujibayashi Y, Yonekura Y, Kawai K, et al. Basic studies on I-123-beta-methyl-R-iodophenylpentadecanoic acid (BMIPP) for myocardial functional diagnosis: effect of beta-oxidation inhibitor. Jpn J Nucl Med 1988;25:1131•5.
Hosokawa R, Nohara R, Fujibayashi Y, et al. Myocardial metabolism of 123 I-BMIPP in a canine model with ischemia: implications of perfusion-metabolism mismatch on SPECT images in patients with ischemic heart disease. J Nucl Med 1999;40:471•8.
Tamaki N, Kawamoto M, Yonekura Y, et al. Regional metabolic abnormality in relation to perfusion and wall motion in patients with myocardial infarction: assessment with emission tomography using iodinated branched fatty acid analog. J Nucl Med 1992;33:659•67.
Franken PR, De Geeter F, Dendale P, et al. Abnormal free fatty acid uptake in subacute myocardial infarction after coronary thrombolysis: correlation with wall motion and inotropic reserve. J Nucl Med 1994;35:1758•65.
Hanaoka S, Yamabe H, Abe H, et al. Improved uptake of fatty acid in metabolically stunned myocardium during dobutamine infusion after myocardial infarction. Circulation 1996;94:I-61.
Hosokawa R, Nohara R, Fujibayashi Y, et al. Myocardial kinetics of iodine-123-BMIPP in canine myocardium after regional ischemia and reperfusion: implications for clinical SPECT. J Nucl Med 1997;38:1857•63.
Hosokawa R, Nohara R, Fujibayashi Y, et al. Metabolic fate of iodine-123 BMIPP in canine myocardium after administration of etomoxir. J Nucl Med 1996;37:1836•40.
Hale SL, Alker KJ, Kloner RA. Evaluation of non-radioactive, colored microspheres for measurement of regional myocardial blood flow in dogs. Circulation 1988;78:428•34.
Hartley CJ, Latson LA, Michael LH, et al. Doppler measurement of myocardial thickening with a single epicardial transducer. Am J Physiol 1983;245:H1066•72.
Fujibayashi Y, Nohara R, Hosokawa R, et al. Metabolism and kinetics of iodine-123-BMIPP in canine myocardium. J Nucl Med 1996; 37:757•61.
Folch J, Lees M. Proteolipides, a new type of tissue lipoproteins. J Biol Chem 1951;191:807•17.
Tateno M, Tamaki N, Kudoh T, et al. Assessment of fatty acid uptake in ischemic heart disease without myocardial infarction. J Nucl Med 1996;37:1981•5.
Pierard LA, De Landsheere CM, Berthe C, et al. Identification of viable myocardium by echocardiography during dobutamine infusion in patients with myocardial infarction after thrombolytic therapy: comparison with positron emission tomography. J Am Coll Cardiol 1990;15:1021•31.
La Canna G, Alfieri O, Giubbini R, et al. Echocardiography during infusion of dobutamine for identification of reversible dysfunction in patients with chronic coronary artery disease. J Am Coll Cardiol 1994;23:617•26.
Fujiwara S, Takeishi Y, Atsumi H, et al. Fatty acid metabolic imaging with iodine-123-BMIPP for the diagnosis of coronary artery disease. J Nucl Med 1997;38:175•80.
De Geeter F, Caveliers V, Pansar I, et al. Effect of oral glucose loading on the biodistribution of BMIPP in normal volunteers. J Nucl Med 1998;39:1850•6.
Caveliers V, De Geeter F, Pansar I, et al. Effect of exercise induced hyperlactatemia on the biodistribution and metabolism of iodine-123-15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid in normal volunteers. Eur J Nucl Med 2000;27:33•40.
Matsunari I, Saga T, Taki J, et al. Kinetics of iodine-123-BMIPP in patients with prior myocardial infarction: assessment with dynamic rest and stress images compared with stress thallium-201 SPECT. J Nucl Med 1994;35:1279•85.
Takeda K, Saito K, Makino K, et al. Iodine-123-BMIPP myocardial washout and cardiac work during exercise in normal and ischemic hearts. J Nucl Med 1997;38:559•63.
Acknowledgements
We thank Keith A. Takechi for reading the manuscript and Naoko Takemoto for secretarial assistance throughout the study. We also thank Nihon Medi-Physics Co. Ltd (Tokyo, Japan) for product support and encouragement.
Author information
Authors and Affiliations
Corresponding author
Additional information
An erratum to this article can be found at http://dx.doi.org/10.1007/s00259-005-1782-3
Rights and permissions
About this article
Cite this article
Hosokawa, R., Nohara, R., Hirai, T. et al. Myocardial metabolism of 123I-BMIPP under low-dose dobutamine infusion: implications for clinical SPECT imaging of ischemic heart disease. Eur J Nucl Med Mol Imaging 32, 75–83 (2005). https://doi.org/10.1007/s00259-004-1622-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00259-004-1622-x