Summary
Iodinated fatty acids (FAs) are now used in Nuclear Medicine to assess, by external detection, myocardial metabolism. Methylated FAs have been proposed as tracers of FA myocardial uptake. IMPPA is a new FA analogue in which a methyl group have been introduced in β position to inhibit β-oxidation and a terminal phenyl group prevents a possible omega oxidation. We have compared the intramyocardial behaviour of this FA with the 15-p-iodophenyl-pentadecanoic acid (IPPA), the straight chain analogue, and with the 15-phenyl-β-methylpentadecanoic acid (MPPA), the 3 of them being labelled with C14 on the carboxyl group, in isolated rat hearts perfused in a recirculating system.
When IMPPA is compared to IPPA (influence of the methyl group), we observe 1 — an inhibition of β-oxidation (no significant production of labelled CO2 and very low radioactivity in the aqueous phase) leading to a reduced uptake, 2 — a lower radioactivity in the organic phase due to a hindrance to the esterification process both into TGs and PLs, the free FAs level being higher. When IMPPA is compared to MPPA (influence of the iodine atom), we observe 1 — the same inhibition of β-oxidation, 2 — a higher myocardial radioactivity due to a much higher level of free FAs, the esterification into TGs and PLs being reduced.
This study with IMPPA indicates that it is taken up by the heart and trapped there, as it is not oxydized. This long retention time, apart from giving good scintigraphic images, should make IMPPA useful to study the regional myocardial uptake of FAs.
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References
Bing RJ, Siegel A, Ungar J, Gilbert M: Metabolism of the human heart. II. Studies on fat, ketone and amino acid metabolism. Am J Med 16: 504–528, 1954
Livni E, Elmaleh DR, Levy S, Brownell GL, Strauss WH: Beta-methyl (1–11C) heptadecanoic acid: a new myocardial metabolic tracer for positron emission tomography. J Nucl Med 23: 169–175, 1982
Goodman MM, Kirsch G, Knapp Jr FF: Synthesis of radioiodinated omega-(p-iodophenyl)-substituted methyl-branched long-chain fatty acids. J Lab Compds Radiopharm XIX: 1316–1318, 1982
Goodman MM, Kirsch G, Knapp Jr FF: Synthesis and evaluation of radio-iodinated terminal p-iodophenyl-substited alpha- and β-methyl-branched fatty acids. J Med Chem 25: 390–397, 1984
Livni E, Elmaleh DR, Barlai-Kowach MM, et al Radioiodinated b-methylphenyl fatty acid as potential tracer for myocardial imaging and metabolism. Eur Heart J (suppl B) 6: 85–89, 1985
Otto CA, Brown LE, Wieland DM, Beierwaltes WH: Radioiodinated fatty acids for myocardial imaging: effects of chain length. J Nucl Med 22: 613–618, 1981
Otto CA, Brown LE, Scott AM: Radioiodinated branchedchain fatty acids: substrates for β-oxidation? Concise communication. J Nucl Med 25: 75–80, 1984
Goodmann MM, Callahan AP, Knapp Jr FF: Design, synthesis and evaluation of omega-iodovinyl and omega-iodoalkyl-substituted methyl-branched fatty acids. J Med Chem 28: 807–814, 1985
Yonekura Y, Brill AB, Som P, Yamamoto K, Srivastava SC, Iwai J, Elmaleh DR, Livni E, Strauss HW, Goodmann MM, Knapp Jr FF: Regional myocardial sustrate uptake in hypertensive rats: a quantitative autoradiographic measurement. Science 227: 1494–1496, 1985
Yamamoto K, Som P, Brill AB, Yonekura Y, Srivastava SC, Meinken GE, Iwai J, Goodmann MM, Knapp Jr FF, Elmaleh DR, Livni E, Strauss HW: Dual tracer autoradiographic study of β-methyl-(1–14C) heptadecanoic acid and 15-p-(131I)-iodophenyl-β-methylpentadecanoic acid in normotensive and hypertensive rats. J Nucl Med 27: 1178–1183, 1986
Keriel C, Marti Batlle D, Le Bars D, Mathieu JP, Comet M, Cuchet P: Are iodinated fatty acids good tracers of myocardial metabolism? IHA vs IPPA. A study on rat heart with 14C labeled fatty acids. Nuclear Medicine (in press)
Reske SN, Sauer W, Machulla HJ, Winkler C: 15-p-(123I) iodophenylpentadecanoic acid as tracer of lipids metabolism: comparison with (1–14C) palmitic acid in murine tissues. J Nucl Med 25: 1335–1342, 1984
Le Bars D, Luu-Duc C, Leo PM, Apparu M, Vidal M, Comet M: Synthesis of 15-(p-iodophenyl) pentadecanoic acid labelled with carbon 14. Appl Radiat Isot 37 (3): 256–257, 1986
Humbert T, Luu-Duc C, Marsura A, Le Bars D, Apparu M, Vidal M: Synthesis of 3-methyl 15-phenyl pentadecanoic acid labelled with carbon 14 to study myocardium metabolism. J Lab Compds Radiophar, (in press)
Humbert T, Luu-Duc C, Marsura A, Le Bars D: Synthesis of 3-methyl 15-p-iodophenylpentadecanoic acid labelled with carbon 14 to study uptake in the myocardium. J Lab Compds Radiophar (submitted to publication)
Bligh EG, Dyer WJ: A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37: 911–917, 1959
Vasdev SC, Kako KJ: Metabolism of erucic acid in the isolated perfused rat heart. Biochim Biophys Acta 431: 22–32, 1976
Van der Vusse GJ, Roemen THM, Flameng W, Reneman RS: Serum-myocardium gradients of non-esterified fatty acids in dog, rat, man. Biochim Biophys Acta 572: 361–370, 1983
Ambrose KR, Owen BA, Goodmann MM, Knapp Jr FF: Evaluation of the metabolism in rat hearts of two new radioiodinated 3-methyl-branched fatty acid myocardial imaging agent. Eur J Nucl Med 12: 486–491, 1987
Knapp Jr FF, Goodmann MM, Callahan AP, Kirsh G: Radioiodinated 15-(p-iodophenyl)-3,3-dimethyl pentadecanoic acid: a useful new agent to evaluate myocardial fatty acid uptake. J Nucl Med 27: 521–531, 1986
Fagret D, Wolf JE, Pilichowski P, Mathieu JP, Pernin C, Apparu M, Arvieux Ch, Cuchet P, Comet M, Vidal M: Iodomethylated fatty acid metabolism in mice and dogs. Eur J Nucl Med (in press)
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Humbert, T., Keriel, C., Batlle, D.M., Luu-Duc, C., Comet, M., Cuchet, P. (1989). Intramyocardial fate of 15-p-iodophenyl-β-methylpentadecanoic acid (IMPPA): Is it a good tracer of fatty acid myocardial uptake?. In: Van Der Vusse, G.J. (eds) Lipid Metabolism in Normoxic and Ischemic Heart. Developments in Molecular and Cellular Biochemistry, vol 5. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-1611-4_29
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DOI: https://doi.org/10.1007/978-1-4613-1611-4_29
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