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Quantitative comparison of transport and phosphorylation of three fluorosugars in the isolated rat heart

Conference · · J. Nucl. Med.; (United States)
OSTI ID:6842176

Bolus injection and coincidence counting of residue curves in an intact isolated rat heart preparation were used for the quantitative comparison of myocardial cell membrane transport and myocardial phosporylation rates of the F-18 labeled fluorosugars 2-deoxy-2-fluoro-D-glucose (2FDG), 3-deoxy-3-fluoro-D-glucose (D-3FDG), and 3-deoxy-3-fluor-L-glucose (L-3FGD). Transport and phosphorylation rates were quantitated using a compartmental model incorporating interstitial and cellular sugar and cellular sugar-6-phosphate. Affinity of cell membrane carrier molecules for D-3FDG was about half that for 2FDG, and transport of both fluorosugars was inhibited by increased glucose concentration. Phosphorylation rate of glucose was determined simultaneously from the rate of release of tritiated water from 2-(H-3)-glucose dissolved in the perfusion medium. Phosphorylation lumped constants of 2FDG and D-3FDG averaged 0.99 +- 0.05 and 0.10 +- 0.01 respectively, and phosphorylation of both analogs clearly demonstrated competition with glucose in the perfusion medium. The rate of phosphatase catalysed hydrolysis of D-3FDG-6-phosphate was twice that of 2FDG-6-phosphate. This, along with the reduced phosphorylation rate, strongly moderates the accumulation of 3FDG-6-phosphate in tissue. Kinetics of L-3FDG were independent of perfusate glucose concentration, and were consistent with access to the cell interior only by simple diffusion. However, fitting of L-3FDG residue curves unexpectedly but unambiguously required three tissue compartments.

Research Organization:
Medical Physics Dept., Univ. of Wisconsin, Madison, WI
OSTI ID:
6842176
Report Number(s):
CONF-840619-
Journal Information:
J. Nucl. Med.; (United States), Journal Name: J. Nucl. Med.; (United States) Vol. 25:5; ISSN JNMEA
Country of Publication:
United States
Language:
English