Annals of Nuclear Medicine

, Volume 14, Issue 1, pp 69–74

Preliminary evaluation of [1-11C]octanoate as a PET tracer for studying cerebral ischemia: A PET study in rat and canine models of focal cerebral ischemia

  • Yuji Kuge
  • Hidefumi Kawashima
  • Tadatoshi Hashimoto
  • Mitsuaki Imanishi
  • Mie Shiomi
  • Kazuo Minematsu
  • Yasuhiro Hasegawa
  • Takenori Yamaguchi
  • Yoshihiro Miyake
  • Naoto Hashimoto
Short Communications

Abstract

Octanoate is taken up into the brain and is converted in astrocytes to glutamine through the TCA cycle after β-oxidation. We speculate that [1-11C]octanoate may be used as a tracer for astroglial functions and/or fatty acid metabolism in the brain and may be useful for studying cerebral ischemia. In the present study we investigated brain distribution of [1-11C]octanoate and compared it with cerebral blood flow (CBF) by using rat and canine models of middle cerebral artery (MCA) occlusion and a high resolution PET. In rats brain distribution of [15O]H2O measured 1–2 h and 5–6 h after insult was compared with that of [1-11C]octanoate measured 3–4 h after insult. Radioactivity ratios of lesioned to normal hemispheres determined with [15O]H2O were lower than those determined with [1-11C]octanoate. These results were confirmed by a study on a canine model of MCA-occlusion. Twenty-four hours after insult, CBF decreased in the MCA-territory of the occluded hemisphere, whereas normal or higher accumulation of [1-11C]octanoate was observed in the ischemic regions. The uptake of [1-11C]octanoate-derived radioactivity therefore increased relative to CBF in the ischemic regions, indicating that [1-11C]octanoate provides functional information different from CBF. In conclusion, we found that [1-11C]octanoate is a potential radiopharmaceutical for studying the pathophysiology of cerebral ischemia.

Key words

[1-11C]octanoate positron emission tomography cerebral ischemia rat dog 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Heiss W-D, Herholz K. Assessment of pathophysiology of stroke by positron emission tomography.Eur J Nucl Med 21: 455–465, 1994.PubMedCrossRefGoogle Scholar
  2. 2.
    Camsonne R, Crouzel C, Comar D, Mazière M, Prenant C, Sastre J, et al. Synthesis ofN-[11C]-methyl,N-(methyl-1 propyl), (chloro-2 phenyl)-1 isoquinoline carboxamide-3 (PK-11195); a new ligand for peripheral benzodiazepine receptors.J. Label Compds Radiopharm 21: 985–991, 1984.CrossRefGoogle Scholar
  3. 3.
    Pascali C, Luthra SK, Pike VW, Price GW, Ahier RG, Hume SP, et al. The radiosynthesis of [18F]PK-14105 as an alternative radioligand for peripheral type benzodiazepine binding sites.Int J Rad Appl Instrum [A] 41: 477–482, 1990.CrossRefGoogle Scholar
  4. 4.
    Junck L, Jewett DM, Kilbourn MR, Young AB, Kuhl DE. PET imaging of cerebral infarcts using a ligand for the peripheral benzodiazepine binding site.Neurology 40 (suppl. 1): 265, 1990.Google Scholar
  5. 5.
    Ramsay SC, Weiller C, Myers R, Cremer JE, Luthra SK, Lammertsma AA, et al. Monitoring by PET of macrophage accumulation in brain after ischemic stroke.Lancet 339: 1054–1055, 1992.PubMedCrossRefGoogle Scholar
  6. 6.
    Oldendorf WH. Carrier-mediated blood-brain barrier transport of short-chain monocarboxylic organic acids.Am J Physiol 224: 1450–1453, 1973.PubMedGoogle Scholar
  7. 7.
    Rowley H, Collins RC. [1-14C]Octanoate: a fast functional marker of brain activity.Brain Res 335: 326–329, 1985.PubMedCrossRefGoogle Scholar
  8. 8.
    Spector R. Fatty acid transport through the blood-brain barrier.J Neurochem 50: 639–643, 1988.PubMedCrossRefGoogle Scholar
  9. 9.
    Cremer JE, Teal HM, Heath DF, Cavanagh JB. The influence of portocaval anastomosis on the metabolism of labeled octanoate, butyrate and leucine in rat brain.J Neurochem 28: 215–222, 1977.PubMedCrossRefGoogle Scholar
  10. 10.
    Auestad N, Korsak RA, Morrow JW, Edmond J. Fatty acid oxidation and ketogenesis by astrocytes in primary culture.J Neurochem 56: 1376–1386, 1991.PubMedCrossRefGoogle Scholar
  11. 11.
    Edmond J, Robbins RA, Bergstrom JD, Cole RA, de Vellis J. Capacity for substrate utilization in oxidative metabolism by neurons, astrocytes and oligodendrocytes from developing brain in primary culture.J Neurosci Res 18: 551–561, 1987.PubMedCrossRefGoogle Scholar
  12. 12.
    Edmond J. Energy metabolism in developing brain cells.Can J Physiol Pharmacol 70: S118-S129, 1992.PubMedGoogle Scholar
  13. 13.
    Norenberg MD, Martinez-Hernandez A. Fine structural localization of glutamine synthetase in astrocytes of rat brain.Brain Res 161: 303–310, 1979.PubMedCrossRefGoogle Scholar
  14. 14.
    Kuge Y, Yajima K, Kawashima H, Yamazaki H, Hashimoto N, Miyake Y. Brain uptake and metabolism of [1-11C]octanoate in rats: pharmacokinetic basis for its application as a radiopharmaceutical for studying brain fatty acid metabolism.Ann Nucl Med 9: 137–142, 1995.PubMedGoogle Scholar
  15. 15.
    Kuge Y, Kawashima H, Yamazaki S, Hashimoto N, Miyake Y. [1-11C]Octanoate as a potential PET tracer for studying glial functions: PET evaluation in rats and cats.Nucl Med Biol 23: 1009–1012, 1996.PubMedCrossRefGoogle Scholar
  16. 16.
    Yamazaki S, Fukui K, Kawashima H, Kuge Y, Miyake Y, Kangawa K. Uptake of radioactive octanoate in astrocytoma cells: basic studies for application of [11C]octanoate as a PET tracer.Ann Nucl Med 10: 395–399, 1996.PubMedGoogle Scholar
  17. 17.
    Ishiwata K, Ishii K, Ogawa K, Sasaki T, Toyama H, Ishii S, et al. Synthesis and preliminary evaluation of [1-11C]hexanoate as a PET tracer of fatty acid metabolism.Ann Nucl Med 9: 51–57, 1995.PubMedCrossRefGoogle Scholar
  18. 18.
    Ishiwata K, Ishii K, Ogawa K, Nozaki T, Senda M. A brain uptake study of [1-11C]hexanoate in the mouse: the effect of hypoxia, starvation and substrate competition.Ann Nucl Med 10: 265–270, 1996.PubMedGoogle Scholar
  19. 19.
    Sakiyama Y, Ishiwata K, Ishii K, Oda K, Toyama H, Ishii S, et al. Evaluation of the brain uptake properties of [1-11C]labeled hexanoate in anesthetized cats by means of positron emission tomography.Ann Nucl Med 10: 361–366, 1996.PubMedGoogle Scholar
  20. 20.
    Fowler JS, Gatiagher BM, MacGregor RR, Wolf AP. Carbon-11 labeled aliphatic amines in lung uptake and metabolism studies: potential for dynamic measurementsin vivo.J Pharmacol Exp Ther 198: 133–145, 1976.PubMedGoogle Scholar
  21. 21.
    Wienhard K, Dahlbom M, Eriksson L, Michel C, Bruckbauer T, Pietrzyk U, et al. The ECAT EXACT HR: performance of a new high resolution positron scanner.J Comput Assist Tomogr 18: 110–118, 1994.PubMedCrossRefGoogle Scholar
  22. 22.
    Kuge Y, Minematsu K, Yamaguchi T, Miyake Y. Nylon monofilament for intraluminal middle cerebral artery occlusion in rats.Stroke 26: 1655–1658, 1995.PubMedGoogle Scholar
  23. 23.
    Minematsu K, Li L, Fisher M, Sotak CH, Davis MA, Fiandaca MS. Diffusion-weighted magnetic resonance imaging: rapid and quantitative detection of focal brain ischemia.Neurology 42: 235–240, 1992.PubMedCrossRefGoogle Scholar
  24. 24.
    De Ley G, Weyne J, Demeester G, Stryckmans K, Goethals P. Van de Velde E, et al. Experimental thromboembolic stroke studied by positron emission tomography: immediate versus delayed reperfusion by fibrinolysis.J Cereb Blood Flow Metab 8: 539–545, 1988.PubMedGoogle Scholar
  25. 25.
    Sakurada O, Kennedy C, Jehle J, Brown JD, Carbin GL, Sokoloff L. Measurement of local cerebral blood flow with iodo[14C]antipyrine.Am J Physiol 234: H59-H66, 1978.PubMedGoogle Scholar
  26. 26.
    Litton J-E, Holte S, Eriksson L. Evaluation of the Karolinska new positron camera system; the Scanditronix PC-2048-15B.IEEE Trans Nucl Sci 37: 743–748, 1990.CrossRefGoogle Scholar
  27. 27.
    Ingvar M, Eriksson L, Rogers GA, Stone-Elander S, Widen L. Rapid feasibility studies of tracer for positron emission tomography: high-resolution PET in small animals with kinetic analysis.J Cereb Blood Flow Metab 11: 926–931, 1991.PubMedGoogle Scholar
  28. 28.
    Brownell AL, Kano M, McKinstry RC, Moskowitz MA, Rosen BR, Brownell GL. PET and MR studies of experimental focal stroke.J Comput Assist Tomogr 15: 376–380, 1991.PubMedCrossRefGoogle Scholar
  29. 29.
    Kuge Y, Minematsu K, Hasegawa Y, Yamaguchi T, Mori H, Matsuura H, et al. Positron emission tomography for quantitative determination of glucose metabolism in normal and ischemic brains in rats: an insoluble problem by the Harderian Glands.J Cereb Blood Flow Metab 17: 116–120, 1997.PubMedCrossRefGoogle Scholar
  30. 30.
    Kuge Y, Miyake Y, Minematsu K, Yamaguchi T, Hasegawa Y. Effects of extracranial radioactivity on measurement of cerebral glucose metabolism by rat-PET with [18F]-2-fluoro-2-deoxy-D-glucose.J Cereb Blood Flow Metab 17: 1261–1262, 1997.PubMedCrossRefGoogle Scholar
  31. 31.
    Yamamura N, Magata M, Kitano H, Konishi J, Saji H. Evaluation of [1-11C]octanoate as a new radiopharmaceutical for assessing liver function using positron emission tomography.Nucl Med Biol 25: 467–472, 1998.PubMedCrossRefGoogle Scholar
  32. 32.
    Kawashima H, Yajima K, Kuge Y, Hashimoto N, Miyake Y. Synthesis of [1-11C]-2-octynoic acid, [1-11C]-2-decynoic acid and [1-11C]-3-(R,S)-methyloctanoic acid as potential markers for PET studies of fatty acid metabolism.J Label Compds Radiopharm 39: 181–193, 1997.CrossRefGoogle Scholar
  33. 33.
    Kawashima H, Kuge Y, Yajima K, Miyake Y, Hashimoto N. Development of step-specific PET tracers for studying fatty acid β-oxidation: biodistribution of [1-11C]octanoate analogs in rats and a cat.Nucl Med Biol 25: 543–548, 1998.PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2000

Authors and Affiliations

  • Yuji Kuge
    • 1
    • 4
  • Hidefumi Kawashima
    • 1
  • Tadatoshi Hashimoto
    • 2
  • Mitsuaki Imanishi
    • 2
  • Mie Shiomi
    • 2
  • Kazuo Minematsu
    • 3
  • Yasuhiro Hasegawa
    • 3
  • Takenori Yamaguchi
    • 3
  • Yoshihiro Miyake
    • 1
  • Naoto Hashimoto
    • 1
  1. 1.Institute for Biofunetional Research Co., Ltd.SapporoJapan
  2. 2.Takeda Chemical Industries Co., Ltd.SapporoJapan
  3. 3.Cerebrovascular Division, Department of MedicineNational Cardiovascular CenterSapporoJapan
  4. 4.Department of Tracer KineticsHokkaido University School of MedicineSapporoJapan

Personalised recommendations