Characteristic brain distribution of 1-(14)C-octanoate in a rat model of focal cerebral ischemia in comparison with those of (123)I-IMP and (123)I-iomazenil

J Nucl Med. 2003 Jul;44(7):1168-75.

Abstract

1-(11)C-Octanoate is a potential tracer for studying astroglial function in PET. To evaluate the usefulness of 1-(11)C-octanoate for studying ischemic stroke, we investigated the brain distribution of 1-(14)C-octanoate and compared it with N-isopropyl-p-(123)I-iodoamphetamine ((123)I-IMP) distribution (cerebral blood flow), (123)I-iomazenil ((123)I-IMZ) distribution (neuronal viability based on (123)I-IMZ binding to benzodiazepine receptors), and hematoxylin-eosin stain (morphologic changes) in a rat model of focal cerebral ischemia.

Methods: The right middle cerebral artery of each rat was occluded intraluminally. The brain distribution of 1-(14)C-octanoate and (123)I-IMP (or (123)I-IMZ) was determined 4 and 24 h after the insult using a dual-tracer autoradiographic technique (n = 4-7 in each group). Coronal brain sections adjacent to those used for autoradiography were stained with hematoxylin and eosin. Regions of interest (ROIs) were determined for 3 coronal slices, and asymmetry indices (AIs, lesion/normal hemisphere) of the tracer uptake were calculated. ROIs on the hemisphere with the lesion were classified into 4 groups: In region A, widespread necrotic cells were observed; in region B, necrotic cells were occasionally observed; in region C1, no morphologic changes were observed and the AIs for (123)I-IMP (or (123)I-IMZ) were <or=0.8; and in region C2, no morphologic changes were observed and the AIs for (123)I-IMP (or (123)I-IMZ) were >0.8.

Results: 1-(14)C-Octanoate uptake decreased in the regions where morphologic changes were observed (regions A and B) but was relatively preserved in the surrounding region without morphologic changes despite reduced (123)I-IMP and (123)I-IMZ uptake (region C1). In the region without morphologic changes (region C1), AIs for 1-(14)C-octanoate were significantly higher than those for (123)I-IMP (4 h, 0.73 +/- 0.23 for 1-(14)C-octanoate and 0.37 +/- 0.20 for (123)I-IMP, P < 0.0001; 24 h, 0.84 +/- 0.11 for 1-(14)C-octanoate and 0.44 +/- 0.15 for (123)I-IMP, P < 0.0001) and those for (123)I-IMZ (4 h, 0.83 +/- 0.19 for 1-(14)C-octanoate and 0.57 +/- 0.13 for (123)I-IMZ, P < 0.0001; 24 h, 0.91 +/- 0.13 for 1-(14)C-octanoate and 0.73 +/- 0.06 for (123)I-IMZ, P < 0.0001).

Conclusion: 1-(14)C-Octanoate uptake was relatively preserved in the regions without morphologic changes despite reduced (123)I-IMP and (123)I-IMZ uptake. 1-(11)C-Octanoate may provide further functional information on the pathophysiology of ischemic stroke, reflecting astroglial function based on fatty acid metabolism.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Animals
  • Autoradiography / methods
  • Brain / metabolism*
  • Brain / pathology
  • Brain Ischemia / metabolism*
  • Brain Ischemia / pathology
  • Caprylates / pharmacokinetics*
  • Disease Models, Animal
  • Flumazenil / analogs & derivatives*
  • Flumazenil / pharmacokinetics*
  • Iofetamine / pharmacokinetics*
  • Radiopharmaceuticals / pharmacokinetics
  • Rats
  • Rats, Sprague-Dawley
  • Tissue Distribution

Substances

  • Caprylates
  • Radiopharmaceuticals
  • Flumazenil
  • iomazenil
  • Iofetamine
  • octanoic acid