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The development of radioiodinated 3-methyl-branched fatty acids for evaluation of myocardial disease by single photon techniques

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Noninvasive Imaging of Cardiac Metabolism

Abstract

The measurement of regional myocardial “release-rates” after intravenous administration of iodine-123-labeled fatty acids such as 17-iodoheptadecanoic acid (HDA) [1–6] and 15-(p-iodophenyl)pentadecanoic acid (IPP) [7–13] has been well documented. These agents have proven useful to probe regional aspects of fatty acid metabolism in ischemic heart disease. Studies with (123I)HDA have als shown an unusual and unexpected relation between uptake and release rates in cardiomyopathies [14]. These agents were designed to exhibit extraction similar to natural fatty acids and enter the β-oxidation catabolic chain. Since free radioiodide and short-chain metabolites are released rapidly, the measurement of regional “release-rates” is presumed to reflect the metabolic activity of the myocardial tissue. The structures of these agents and structurally-modified fatty acids discussed in this chapter are shown in Figure 1.

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References

  1. Feinendegen L F, Vyska K, Freunlieb C et al. (1981) Noninvasive analysis of metabolic reactions in body tissues, the case of myocardial fatty acids. Eur J Nucl Med 6: 191–200

    Article  PubMed  CAS  Google Scholar 

  2. Machulla H-J, Stoecklin G, Kupfernagel C etal (1978) Comparative evaluation of fatty acids labeled with C-11, Cl-34m, Br-77, and I-123 for metabolic studies of the myocardium: Concise communication. J Nucl Med 19: 298–302

    PubMed  CAS  Google Scholar 

  3. Freundlieb C, Hock A, Vyska K et al (1980) Myocardial imaging and metabolic studies with 17-(123I)iodoheptadecanoic acid. J Nucl Med 21: 1043–1050

    PubMed  CAS  Google Scholar 

  4. van der Wall E E, Heidendal G A K, den Hollander W et al (1981) Metabolic myocardial imaging with I23I-labeled heptadecanoic acid in patients with angina pectoris. Eur J Nucl Med 6: 391–396

    PubMed  Google Scholar 

  5. van der Wall E E, den Hollander W, Heidendal G A K et al (1981) Dynamic myocardial scintigraphy with 123I-labeled free fatty acids in patients with myocardial infarction. Eur J Nucl Med 6: 383–389

    PubMed  Google Scholar 

  6. Dudczak R, Kletter K, Frischauf H, Schmolinger R, Derfler K, Losert U.(1982) Myocardial turnover rates of I-123-heptade canoic acid (HDA) and (pIPPA). Rad Isot Klin und Forschung 15: 685–696

    CAS  Google Scholar 

  7. Machulla H-J, Marsmann M, Dutschka K (1980) Biochemical concept and synthesis of a radioiodinated phenyl fatty acid for in vivo metabolic studies of the myocardium. Eur J Nucl Med 5: 171–173

    Article  PubMed  CAS  Google Scholar 

  8. Reske S N, Machulla H-J, Winkler C (1982) Metabolism of 15-p-(I-123)-phenyl)pentadecanoic acid (IP) in hearts of rats. J Nucl Med 23: P10

    Google Scholar 

  9. Reske S N, Simon H, Machulla H-J, Biersak H J et al (1982) Myocardial turnover of p-(I-123-phenyl)-pentadecanoic acid (IP) in patients with CAD. J Nucl Med 23: P34

    Google Scholar 

  10. Dudczak R, Hofer R (1983) Myocardial scintigraphy with 123I-labeled fatty acids. Summary of round table discussion. J Radioanalyt Chem 79: 329–336

    Article  Google Scholar 

  11. Dudczak R, Schmoliner R, Kletter K et al (1983) Clinical evaluation of 123I-labeled p-phenyl- pentadecanoic acid (p-IPPA) for myocardial scintigraphy. J Nucl Med All Sci 27: 267–279

    CAS  Google Scholar 

  12. Dudczak R (1983) Myokardszintigraphie mit jod-123-markierten Fettsauren. Wien Klin Wochenschr 95: 4–35

    Google Scholar 

  13. Dudczak R, Kletter K, Frischauf H et al (1984) The use of 123I-labeled heptadecanoic acid (HDA) as metabolic tracer: Preliminary report. Eur J Nucl Med 9: 81–85

    Article  PubMed  CAS  Google Scholar 

  14. Höck A, Freundlieb C, Vyska K et al (1983) Myocardial imaging and metabolic studies with [17-(123I)]iodoheptadecanoic acid in patients with idiopathic congestive cardiomyopathy. J Nucl Med 24: 22–28

    PubMed  Google Scholar 

  15. Bing R J, Sigel A, Unger J et al. (1954) Metabolism of the human heart. Am J Med 16: 504–515

    Article  PubMed  CAS  Google Scholar 

  16. Ballard F B, Danforth W H, Naegel S et al (1960) Myocardial metabolism of fatty acids. J Clin Invest 39: 717–723

    Article  PubMed  CAS  Google Scholar 

  17. Evans J R, Gunton R W, Baker R G et al (1965) Use of radioiodinated fatty acid for photoscans of the heart. Circ Res 16: 1–10

    PubMed  CAS  Google Scholar 

  18. Gunton R W, Evans J R, Baker R G et al (1965) Demonstration of myocardial infarction by photoscans of the heart in man. Am J Cardiol 16: 482–487

    Article  PubMed  CAS  Google Scholar 

  19. Poe N D (1977) Rationale and radiopharmaceuticals for myocardial imaging. Semin Nucl Med 7: 7–14

    Article  PubMed  CAS  Google Scholar 

  20. Poe N D, Robinson G D, Zielinski F W et al (1977) Myocardial imaging with I-123-hexade- cenoic acid. Radiology 124: 419–424

    PubMed  CAS  Google Scholar 

  21. Poe N D, Eber L M, Normann A S et al (1977) Myocardial images in nonacute coronary and noncoronary heart diseases. J Nucl Med 18: 18–23

    PubMed  CAS  Google Scholar 

  22. Robinson G D (1977) Synthesis of 123-I-16-iodo-9-hexadecenoic acid and derivatives for use as myocardial perfusion imaging agents. Int J Appl Rad Isot 28: 149–156

    Article  CAS  Google Scholar 

  23. Weiss E S, Hoffman E J, Phelps M E et al (1976) External detection and visualization of myocardial ischemia with 11C-substrates in vivo and in vitro. Circ Res 39: 24–32

    PubMed  CAS  Google Scholar 

  24. Schön H R, Schelbert H R, Robinson G et al (1982) C-11 labeled palmitic acid for noninvasive evaluation of regional myocardial fatty acid metabolism with positron-computed tomography. Am Heart J 103: 532–547

    Article  PubMed  Google Scholar 

  25. Robinson C D, Lee A W (1975) Radioiodinated fatty acids for heart imaging: Iodine monochloride addition compared with iodine replacement labeling. J Nucl Med 16: 17–21

    PubMed  CAS  Google Scholar 

  26. Okada R D, Elmaleh D E, Werre G S et al (1983) Myocardial kinetics of I-123-labeled 16-hexadecanoic acid. Eur J Nucl Med 8: 211–217

    Article  PubMed  CAS  Google Scholar 

  27. Elmaleh D R, Knapp F F Jr, Yasuda T et al (1981) Myocardial imaging with 9-[Te-123]mtelluraheptadecanoic acid. J Nucl Med 22: 994–999

    PubMed  CAS  Google Scholar 

  28. Knapp F F Jr, Ambrose K R, Callahan A P et al. (1979) Tellurium-123m-labeled isosteres of palmitoleic and oleic acids show high myocardial uptake, Radiopharmaceuticals, Vol II. New York: Society of Nuclear Medicine

    Google Scholar 

  29. Knapp F F Jr, Ambrose K R, Callahan A P et al. (1981) Effects of chain length and tellurium position on the myocardial uptake of Te-123m fatty acids. J Nucl Med 22: 988–993

    PubMed  CAS  Google Scholar 

  30. Knapp F F Jr, Goodman M M, Callahan A P et al (1983) New myocardial imaging agents: stabilization of radioiodine as a terminal vinyl iodide moiety as tellurium fatty acids. J Med Chem 26: 1293–1300

    Article  PubMed  CAS  Google Scholar 

  31. Knapp F F Jr, Goodman M M. The design and biological properties of iodine-123-labeled β-methyl-branched fatty acids. Eur Heart (1985) 6 (Suppl B): 71–83

    CAS  Google Scholar 

  32. Goodman M M, Knapp F F Jr, Callahan A P et al (1982) Synthesis and biological evaluation of 17-(131I)iodo-9-telluraheptadecanoic acid, a potential myocardial imaging agent. J Med Chem 25: 613–618

    Article  PubMed  CAS  Google Scholar 

  33. Okada R D, Knapp F F Jr, Elmaleh D R et al (1982) Tellurium- 123m-labeled-9-telluraheptadecanoic acid: a possible cardiac imaging agent. Circulation 65: 305–310

    Article  PubMed  CAS  Google Scholar 

  34. Bianco J A, Pape L A, Alpert J S, Zheng M, Hnatowich D, Goodman M M, Knapp F F Jr (1984) Accumulation of radioiodinated 15-(p-iodophenyl)-6-tellurapentadecanoic acid in ischemic myocardium during acute coronary occlusion and reperfusion. J Am Coll Cardiol 4: 80–87

    Article  PubMed  CAS  Google Scholar 

  35. Yonekura Y, Tamaki N, Torizuka K et al (1983) Quantitative autoradiographic measurement of regional myocardial substrate uptake in hypertensive rats. J Nucl Med (Abstr) 24: P24

    Google Scholar 

  36. Yonekura Y, Brill A B, Som P, Yamamoto K, Srivastava S C, Iwai J, Elmaleh D R, Livni E, Strauss H W, Goodman M M, Knapp F F Jr (1985) Regional myocardial substrate uptake in hypertensive rats: a quantitative autoradiographic measurement. Science 227: 1494–1496

    Article  PubMed  CAS  Google Scholar 

  37. Yamamato K, Som P, Brill A B (1984) Comparative dual tracer studies of β-methyl-(l-C-14)- heptadecanoic acid and 15-p-(I-131)iodophenyl-β-mehtylpentadecanoic acid (BMPDA) in hypertensive rats. J Nucl Med (Abstr) 25: P31

    Google Scholar 

  38. Goodman M M, Kirsch G, Knapp F F Jr (1982) Synthesis of radioiodinated ω-p-(iodo-phe- nyl)-substituted methyl-branched long-chain fatty acids. J Labeled Compd Radiopharm 19: 1316–1318

    Google Scholar 

  39. Goodman M M, Knapp F F Jr, Callahan A P, Ferren L A (1982) A new, well-retained myocardial imaging agent: radioiodinated 15-(p-iodophenyl)-6-tellurapentadecanoic acid. J Nucl Med 23: 904–908

    PubMed  CAS  Google Scholar 

  40. Goodman M M, Kirsch G, Knapp F F Jr (1984) Synthesis and evaluation of radioiodinated terminal p-iodophenyl-substituted α- and β-methyl-branched fatty acids. J Med Chem 27: 390–397

    Article  PubMed  CAS  Google Scholar 

  41. Goodman M M, Knapp F F Jr, Elmaleh D R, Strauss H W (1984) New myocardial imaging agents: synthesis of 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid by decomposition of a 3,3-(1,5-pentanediyl)triazene precursor. J Org Chem 49: 2322–2325

    Article  CAS  Google Scholar 

  42. Elmaleh D R, Livni E, Levy S et al (1982) Radioiodinated beta methyl omega-phenyltetradecanoic acid (BMTPA): a potential new agent for studies of myocardial fatty acid (FA) metabolism. J Nucl Med (Abstr) 23: P103–P104

    Google Scholar 

  43. Livni E, Elmaleh D R, Levy S et al (1982) Beta-methyl (l-11C)heptadecanoic acid: a new myocardial metabolic tracer for positron emission tomography. J Nucl Med 23: 169–175

    PubMed  CAS  Google Scholar 

  44. Livni E, Elmaleh D R, Schluederberg J et al (1982) A potential new agent for studies of myocardial fatty acid metabolism: 131I-ω-iodophenyl-β-mehtyltetradecanoic acid. In: Nuclear Medicine and Biology Advances, Vol 2. New York: Pergamon, pp 1684–1686

    Google Scholar 

  45. Chien K R, Han A, White J, Kulkarni P (1983) In vivo esterification of a synthetic 125I-labeled fatty acid into cardiac glycolipids. Am J Physiol 254 (Heart Circ Physiol) H693–H697

    Google Scholar 

  46. Knapp F F Jr, Srivastava P C, Callahan A P et al. (1984) Effect of tellurium position on the myocardial uptake of radioiodinated 18-iodotellura-17-octadecanoic acid analogues. J Med Chem 27: 57–63

    Article  PubMed  CAS  Google Scholar 

  47. Bergstrom S, Borgstrom B, Tryding N (1954) Intestinal absorption and metabolism of 2:2-dimethylstearic acid in the rat. Biochem J 58: 604–608

    PubMed  CAS  Google Scholar 

  48. Tryding N (1957) Intestinal absorption and metabolism of 2,2-dimethylstearic acids in man. Ark Kemi 11: 307–312

    CAS  Google Scholar 

  49. Tryding N, Westoo G (1957) On the metabolism of 2,2-dimethyl-nonodecanoic acid in man. Ark Kemi 11: 313–316

    CAS  Google Scholar 

  50. Goodman D S, Steinberg D (1958) Studies of the metabolism of 3,3-dimethylphenyl-myristic acid, a nonoxidizable fatty acid analogue. J Biol Chem 233: 1066–1071

    PubMed  CAS  Google Scholar 

  51. Otto C A, Brown L E, Wieland D M (1981) Structure-distribution study of I-123-ω-iodo fatty acids. J Labeled Cpd Radiopharm 18: 43–44

    Google Scholar 

  52. Otto C A, Brown L E, Wieland DM et al. (1981) Radioiodinated fatty acids for myocardial imaging: effects of chain length. J Nucl Med 22: 613–618

    PubMed  CAS  Google Scholar 

  53. Okada R D, Elmaleh D R, Weisse G S etal. (1983) Myocardial kinetics of 123I-labeled-16-hexadecanoic acid. Eur J Nucl Med 8: 211–217

    Article  PubMed  CAS  Google Scholar 

  54. Kloster G, Stocklin G (1982) Determination of the rate determining step in halofatty acid turnover in the heart. In: Radioaktive Isotope in Klinik und Forschung Band 15, Verlag H Egermann, Wien pp 235–241

    Google Scholar 

  55. Kloster G, Stocklin G, Smith E F et al. (1984) ω-halofatty acids: a probe for mitochondrial membrane integrity - in vitro investigations in normal and ischemic myocardium. Eur J Nucl Med 9: 305–311

    Article  PubMed  CAS  Google Scholar 

  56. Visser F C, Westera G, van Eenige M J et al. (1985) The myocardial elimination rate of radioiodinated heptadecanoic acid. Eur J Nucl Med 10: 118–122

    Article  PubMed  CAS  Google Scholar 

  57. Murad S, Kishimoto Y (1975) α-Hydroxylation of lignoceric acid to cerebronic acid during brain development. J Biol Chem 250(15): 5841–5846

    PubMed  CAS  Google Scholar 

  58. Hajra A K, Radin N S (1963) In vivo conversion of labeled fatty acids to sphingolipid fatty acids in rat brain. J Lipid Res 4: 448–453

    PubMed  CAS  Google Scholar 

  59. Steinberg D, Herndon J H, Unlendorf B W, Mize C E, Avigan J, Milne G W A (1967) Refsum’s disease: Nature of the enzyme defect. Science 156: 1740–1742

    Article  PubMed  CAS  Google Scholar 

  60. Steinberg D, Mize C E, Avigan J (1967) Studies on the metabolic error in Refsum’s disease. J Clin Invest 46: 313–322

    Article  PubMed  CAS  Google Scholar 

  61. Steinberg D, Vroom F Q, Engel W K, Cammermeyer J, Mize C E, Avigan J (1967) Refsum’s disease: A recently characterized lipidosis involving the central nervous systems. Ann Intern Med 66: 393–395

    Google Scholar 

  62. Steinberg D (1972) Phytanic acid storage disease: Refsum’s disease In: Stanbury J B, Wyngaarden J B, Fredrickson D S (eds) The metabolic basis of inherited disease. New York: McGraw-Hill, pp 833–853

    Google Scholar 

  63. Folch J, Lees M, Stanley G H S (1957) A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 226: 497–509

    PubMed  CAS  Google Scholar 

  64. Reske S N, Sauer W, Machulla H-J et al. (1984) 15-(p-(123I)iodophenylpentadecanoic acid as a tracer lipid metabolism-comparison with (1-14C)palmitic acid in murine tissues. J Nucl Med 25: 1335–1342

    PubMed  CAS  Google Scholar 

  65. Braunwald E, Ross J, Sonnenblick E H (1976) Mechanisms of contraction of the normal and failing heart. Boston: Little Brown and Company

    Google Scholar 

  66. Groette G J, Strauss H W et al. (1979) The influence of left ventricular volume and wall motion on myocardial images. Circulation 59: 1172–1177

    Google Scholar 

  67. Fowler J S, MacGregor R R, Wolf A P et al. (1981) A shielder synthesis system for production of 2-deoxy-2[18F]fluoro-D-glucose. J Nucl Med 22: 276–380

    Google Scholar 

  68. Poe N D, Robinson G D, Graham L S et al. (1976) Experimental basis for myocardial imaging with 123I labeled hexadecanoic acid. J Nucl Med 17: 1077–1082

    PubMed  CAS  Google Scholar 

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© 1987 Martinus Nijhoff Publishers, Dordrecht

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Knapp, F.F. et al. (1987). The development of radioiodinated 3-methyl-branched fatty acids for evaluation of myocardial disease by single photon techniques. In: van der Wall, E.E. (eds) Noninvasive Imaging of Cardiac Metabolism. Developments in Cardiovascular Medicine, vol 55. Springer, Dordrecht. https://doi.org/10.1007/978-94-009-3287-6_9

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  • DOI: https://doi.org/10.1007/978-94-009-3287-6_9

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