Abstract
Purpose
18F-Fluorodeoxyglucose (FDG) imaging, provided by current positron emission tomography (PET) systems dedicated to small animals, might provide a precise functional assessment of the left ventricle (LV) in rats, although conventional metabolic conditioning by hyperinsulinaemic glucose clamping is not well adapted to this setting. This study was aimed at assessing cardiac FDG PET in rats pre-medicated with acipimox, a potent nicotinic acid derivative yielding comparable image quality to clamping in man.
Methods
Metabolic conditioning was compared in Wistar rats between a conventional oral glucose loading (1.5 mg/kg) and acipimox, which was given at high but well tolerated doses subcutaneously (25 mg/kg) or orally (50 mg/kg). Myocardial to blood (M/B) activity ratio and myocardial signal to noise (S/N) ratio were analysed on gated FDG PET images.
Results
The S/N ratio of the gated cardiac images evolved in parallel with the M/B activity ratio and these two ratios were independently enhanced by glucose loading and acipimox. However, these enhancements were: (1) dramatic for acipimox, especially for the high oral dose of 50 mg/kg (from 2.85 ± 0.57 to 10.73 ± 0.54 for the M/B ratio of rats with or without glucose loading; p < 0.0001) and (2) much more limited for glucose loading (from 6.61 ± 0.49 to 7.89 ± 0.41 for the M/B ratio of rats with or without acipimox administration; p = 0.049). With the high oral dose of acipimox, the gated cardiac FDG PET images had very high S/N ratios, at least equivalent to those currently documented in man.
Conclusion
Metabolic conditioning by oral doses of acipimox is highly efficient for experimental studies planned with cardiac FDG PET in rats.
Similar content being viewed by others
References
Camici PG. Gated PET and ventricular volume. J Nucl Med 2003;44(10):1662.
Slart RH, Bax JJ, de Jong RM, de Boer J, Lamb HJ, Mook PH, et al. Comparison of gated PET with MRI for evaluation of left ventricular function in patients with coronary artery disease. J Nucl Med 2004;45(2):176–82.
Schaefer WM, Lipke CS, Nowak B, Kaiser HJ, Buecker A, Krombach GA, et al. Validation of an evaluation routine for left ventricular volumes, ejection fraction and wall motion from gated cardiac FDG PET: a comparison with cardiac magnetic resonance imaging. Eur J Nucl Med Mol Imaging 2003;30(4):545–53.
Hesse B, Tägil K, Cuocolo A, Anagnostopoulos C, Bardiés M, Bax J, et al. EANM/ESC procedural guidelines for myocardial perfusion imaging in nuclear cardiology. Eur J Nucl Med Mol Imaging 2005;32(7):855–97.
Bax JJ, Veening MA, Visser FC, van Lingen A, Heine RJ, Cornel JH, et al. Optimal metabolic conditions during fluorine-18 fluorodeoxyglucose imaging; a comparative study using different protocols. Eur J Nucl Med 1997;24(1):35–41.
Knuuti MJ, Yki-Järvinen H, Voipio-Pulkki LM, Mäki M, Ruotsalainen U, Härkönen R, et al. Enhancement of myocardial [fluorine-18]fluorodeoxyglucose uptake by a nicotinic acid derivative. J Nucl Med 1994;35(6):989–98.
Bax JJ, Visser FC, Poldermans D, Van Lingen A, Elhendy A, Boersma E, et al. Safety and feasibility of cardiac FDG SPECT following oral administration of Acipimox, a nicotinic acid derivative: comparison of image quality with hyperinsulinemic euglycemic clamping in nondiabetic patients. J Nucl Cardiol 2002;9(6):587–93.
Schröder O, Hör G, Hertel A, Baum RP. Combined hyperinsulinaemic glucose clamp and oral acipimox for optimizing metabolic conditions during 18F-fluorodeoxyglucose gated PET cardiac imaging: comparative results. Nucl Med Commun 1998;19(9):867–74.
Kudo T, Fukuchi K, Annala AJ, Chatziioannou AF, Allada V, Dahlbom M, et al. Noninvasive measurement of myocardial activity concentrations and perfusion defect sizes in rats with a new small-animal positron emission tomograph. Circulation 2002;106(1):118–23.
Thomas D, Bal H, Arkles J, Horowitz J, Araujo L, Acton PD, et al. Noninvasive assessment of myocardial viability in a small animal model: comparison of MRI, SPECT, and PET. Magn Reson Med 2008;59(2):252–9.
Chapon C, Jackson JS, Aboagye EO, Herlihy AH, Jones WA, Bhakoo KK. An in vivo multimodal imaging study using MRI and PET of stem cell transplantation after myocardial infarction in rats. Mol Imaging Biol 2009;11(1):31–8.
Croteau E, Bénard F, Cadorette J, Gauthier ME, Aliaga A, Bentourkia M, et al. Quantitative gated PET for the assessment of left ventricular function in small animals. J Nucl Med 2003;44(10):1655–61.
Nakagawa K, Namba H, Iyo M, Fukushi K, Irie T, Yamanouchi M, et al. Simplified PET quantitation of myocardial glucose utilization. J Nucl Med 1995;36(11):2094–102.
Namba H, Nakagawa K, Iyo M, Fukushi K, Irie T. A simple method for measuring glucose utilization of insulin-sensitive tissues by using the brain as a reference. Eur J Nucl Med 1994;21(3):228–31.
Higuchi T, Nekolla SG, Jankaukas A, Weber AW, Huisman MC, Reder S, et al. Characterization of normal and infarcted rat myocardium using a combination of small-animal PET and clinical MRI. J Nucl Med 2007;48(2):288–94.
Carballo-Jane E, Gerckens LS, Luell S, Parlapiano AS, Wolff M, Colletti SL, et al. Comparison of rat and dog models of vasodilatation and lipolysis for the calculation of a therapeutic index for GPR109A agonists. J Pharmacol Toxicol Methods 2007;56(3):308–16.
Blachère JC, Pérusse F, Bukowiecki LJ. Lowering plasma free fatty acids with Acipimox mimics the antidiabetic effects of the beta 3-adrenergic agonist CL-316243 in obese Zucker diabetic fatty rats. Metabolism 2001;50(8):945–51.
Kemp BJ, Hruska CB, McFarland AR, Lenox MW, Lowe VJ. NEMA NU 2-2007 performance measurements of the Siemens Inveon preclinical small animal PET system. Phys Med Biol 2009;54(8):2359–76.
Visser EP, Disselhorst JA, Brom M, Laverman P, Gotthardt M, Oyen WJ, et al. Spatial resolution and sensitivity of the Inveon small-animal PET scanner. J Nucl Med 2009;50(1):139–47.
Maskali F, Franken PR, Poussier S, Tran N, Vanhove C, Boutley H, et al. Initial infarct size predicts subsequent cardiac remodeling in the rat infarct model: an in vivo serial pinhole gated SPECT study. J Nucl Med 2006;47(2):337–44.
Nishikawa J, Ohtake T, Yokoyama I, Watanabe T, Momose T, Sasaki Y. Simple method to quantify myocardial glucose metabolism from MB ratio in myocardial FDG PET. Ann Nucl Med 1996;10(3):323–8.
Vom Dahl J, Herman WH, Hicks RJ, Ortiz-Alonso FJ, Lee KS, Allman KC, et al. Myocardial glucose uptake in patients with insulin-dependent diabetes mellitus assessed quantitatively by dynamic positron emission tomography. Circulation 1993;88:395–404.
Marie PY, Djaballah W, Franken PR, Vanhove C, Muller MA, Boutley H, et al. OSEM reconstruction, associated with temporal Fourier and depth-dependant resolution recovery filtering, enhances results from sestamibi and 201Tl 16-interval gated SPECT. J Nucl Med 2005;46:1789–95.
Schinkel AF, Bax JJ, Valkema R, Elhendy A, van Domburg RT, Vourvouri EC, et al. Effect of diabetes mellitus on myocardial 18F-FDG SPECT using acipimox for the assessment of myocardial viability. J Nucl Med 2003;44:877–83.
Tuunanen H, Engblom E, Naum A, Någren K, Hesse B, Airaksinen KE, et al. Free fatty acid depletion acutely decreases cardiac work and efficiency in cardiomyopathic heart failure. Circulation 2006;114(20):2130–7.
Nuutila P, Knuuti MJ, Raitakari M, Ruotsalainen U, Teräs M, Voipio-Pulkki LM, et al. Effect of antilipolysis on heart and skeletal muscle glucose uptake in overnight fasted humans. Am J Physiol 1994;267(6 Pt 1):E941–6.
Acknowledgements
The authors thank the FRM (Foundation for Medical Research in France), Lorraine Region and FDF (Foundation of France) for financial support and M. Pierre Pothier for critical review of the manuscript.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Poussier, S., Maskali, F., Tran, N. et al. ECG-triggered 18F-fluorodeoxyglucose positron emission tomography imaging of the rat heart is dramatically enhanced by acipimox. Eur J Nucl Med Mol Imaging 37, 1745–1750 (2010). https://doi.org/10.1007/s00259-010-1418-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00259-010-1418-0