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Operational Lumped Constant for FDG in Normal Adult Male Rats

¹ Positron Emission Tomography Department, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland; ² Institute of Radiology Sciences, University of Milan, Milan, Italy; and ³ Laboratory of Cerebral Metabolism, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland

Correspondence: For correspondence or reprints contact: Louis Sokoloff, MD, National Institutes of Health, Bldg. 49, Room 1B80, 49 Convent Dr., MSC 4415, Bethesda, MD 20892. E-mail: louissokoloff{at}mail.nih.gov

We determined an operational value for the lumped constant to be used in measurements of the local rate of cerebral glucose use (lCMR_glc) with FDG in normal adult male rats. Methods: The standard quantitative autoradiographic method was used with 2-deoxy-D-¹⁴C-glucose (¹⁴C-DG) and with ¹⁴C-FDG in awake normal adult male rats. Timed arterial blood samples were drawn for 45 min after the bolus and assayed for plasma glucose and ¹⁴C concentrations. At the end of the 45-min experimental period, the rats were killed, and their brains were removed and divided in half sagittally. One hemisphere was immediately frozen and assayed for local ¹⁴C concentrations by quantitative autoradiography; the other was weighed, homogenized in t-octylphenoxypolyethoxyethanol solution, and assayed for ¹⁴C concentrations in the whole brain by liquid scintillation counting. Paired rats (3 pairs), one in each pair receiving ¹⁴C-DG and the other receiving ¹⁴C-FDG, were studied in parallel on the same day. Additional unpaired animals (n = 8) were studied with either ¹⁴C-DG or ¹⁴C-FDG but not in parallel on the same day. To calculate the lCMR_glc in rats studied with ¹⁴C-FDG, the rate constants for ¹⁴C-FDG were estimated from the ¹⁴C-DG values determined for rats and the ¹⁴C-FDG/¹⁴C-DG ratios determined for humans. In all of the rats studied with either ¹⁴C-DG or ¹⁴C-FDG, the lCMR_glc was first calculated in 12 representative brain structures with the lumped constant of 0.48 previously determined for ¹⁴C-DG in rats. The ratio of the lCMR_glc thus determined with ¹⁴C-FDG to that determined with ¹⁴C-DG for each structure was then multiplied by the lumped constant for ¹⁴C-DG to estimate the lumped constant for ¹⁴C-FDG. The lCMR_glc and the lumped constant for FDG in the brain as a whole were similarly estimated from the tracer concentrations in the brain homogenates. Results: The mean values for the lumped constant for FDG were found to be 0.71 and 0.70 in the autoradiographic assays and the assays with brain homogenates, respectively. Conclusion: The appropriate value for the lumped constant to be used in determinations of the lCMR_glc in normal adult male rat studies with ¹⁸F-FDG and small-animal PET scanners is 0.71.

Key Words: lumped constant • FDG • rats

COPYRIGHT © 2007 by the Society of Nuclear Medicine, Inc.

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