OtherBASIC SCIENCE INVESTIGATIONS

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

James T. Thackeray, Rob S. Beanlands and Jean N. DaSilva
Journal of Nuclear Medicine October 2007, 48 (10) 1733-1740; DOI: https://doi.org/10.2967/jnumed.107.043570

Article Figures & Data

Figures

  • FIGURE 1. 
    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).

  • FIGURE 2. 
    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.

  • FIGURE 3. 
    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.

  • FIGURE 4. 
    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.

Tables

  • TABLE 1

    Percent Change in HED Uptake After Pharmacologic Treatment in Tissues Exhibiting NET-Specific Retention

    Treatment and doseLeft ventricleBrown adiposeLungPancreas
    Desipramine (n = 7), 10 mg/kg 30 min earlier−89−71−60−50
    Nisoxetine (n = 6), 10 mg/kg 30 min earlier−85−57−53−49
    Metaraminol (n = 6), 1.3 mg/kg intravenous coinjection−88−63−58−54

    • Percent change = ([%ID/g treated] − [%ID/g control])/(%ID/g control) × 100%.

    • Values presented represent significant deviation (P < 0.05) in %ID/g treated as compared with untreated controls.

  • TABLE 2

    Percent Change in HED Uptake After Pharmacologic Treatment to Elevate NE in Tissues Exhibiting NET-Specific Retention

    Treatment and doseLeft ventricleBrown adiposeLungPancreas
    Tranylcypromine
     0.5 mg/kg (n = 9)−30−20+1−36
     1.0 mg/kg (n = 7)−35−36−22−38
     2.0 mg/kg (n = 12)−63−22−17−53
     5.0 mg/kg (n = 3)−75−48−49−47
     10 mg/kg (n = 12)−82−68−52−44
    NE
     0.05 mg/kg/h (n = 6)−53+13−10−16
     0.15 mg/kg/h (n = 10)−68+9−17−23
     0.45 mg/kg/h (n = 9)−80−40−40−29

    • Percent change = ([%ID/g treated] – [%ID/g control])/(%ID/g control) × 100%.

    • All values presented represent significant deviation (P < 0.05) in %ID/g treated as compared with untreated controls except brown adipose tissue and lung (tranylcypromine: 0.5, 1.0, 2.0, 5.0 mg/kg; NE: 0.05, 0.15 mg/kg/h) and pancreas (NE: 0.05 mg/kg/h).

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