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Presence of Specific ¹¹C-meta-Hydroxyephedrine Retention in Heart, Lung, Pancreas, and Brown Adipose Tissue

¹ Cardiovascular PET Molecular Imaging Program, National Cardiac PET Centre, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada; and ² Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada

View larger version (20K): [in this window] [in a new window]   FIGURE 1.  Distribution of HED in myocardium (A) and other peripheral tissues (B) at 15, 30, 45, 60, and 90 min after intravenous injection in rats. Data are shown as mean %ID/g of tissue ± SD (n = 26 at 30 min; n = 6 at 15, 45, 60, and 90 min).

View larger version (14K): [in this window] [in a new window]   FIGURE 2.  Effect of blocking NET-specific HED retention with NE reuptake inhibitor desipramine (10 mg/kg intraperitoneally 30 min earlier) or nisoxetine (10 mg/kg intraperitoneally 30 min earlier) or increasing competition for reuptake with NE analog metaraminol (1.3 mg/kg intravenous coinjection). Animals were sacrificed at 30 min after HED injection. Data are shown as mean %ID/g of tissue ± SD (controls, n = 26; desipramine, n = 7; nisoxetine, n = 6; metaraminol, n = 6); P < 0.0001; *P < 0.05 as compared with controls using 1-way ANOVA with Bonferroni post hoc comparisons.

View larger version (23K): [in this window] [in a new window]   FIGURE 3.  Effect of elevated NE on HED retention by pretreatment with MAO inhibitor tranylcypromine (0.5–10 mg/kg intraperitoneally 1 h earlier) (A) or subcutaneous infusion of NE (0.05–0.45 mg/kg/h, 6 h) (B). Animals were sacrificed at 30 min after HED injection. Data are shown as mean %ID/g of tissue ± SD (tranylcypromine: controls, n = 26; 0.5 mg/kg, n = 9; 1 mg/kg, n = 7; 2 mg/kg, n = 12; 5 mg/kg, n = 3; 10 mg/kg, n = 12; NE: sham, n = 8; 0.05 mg/kg/h, n = 6; 0.15 mg/kg/h, n = 10; 0.45 mg/kg/h, n = 9); P < 0.0001; *P < 0.05 as compared with controls using 1-way ANOVA with Bonferroni post hoc comparisons.

View larger version (11K): [in this window] [in a new window]   FIGURE 4.  Representative HPLC chromatograms of 11C-labeled peaks at 30 min after HED injection in plasma (A), heart (B), brown adipose tissue (C), and pancreas (D). Column and solvents were switched 4–5 min after injection onto HPLC; unchanged HED was eluted at 14 min after column/solvent switch. Radioactivity levels represent total counts and vary, depending on time of analysis due to isotope decay.