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PET Studies of d-Methamphetamine Pharmacokinetics in Primates: Comparison with l-Methamphetamine and (−)-Cocaine

Joanna S. Fowler, Carsten Kroll, Richard Ferrieri, David Alexoff, Jean Logan, Stephen L. Dewey, Wynne Schiffer, David Schlyer, Pauline Carter, Payton King, Colleen Shea, Youwen Xu, Lisa Muench, Helene Benveniste, Paul Vaska and Nora D. Volkow
Journal of Nuclear Medicine October 2007, 48 (10) 1724-1732; DOI: https://doi.org/10.2967/jnumed.107.040279

Article Figures & Data

Figures

  • FIGURE 1. 
    FIGURE 1. 

    Summed brain images for 11C-d-methamphetamine (top row, from 0–90 min) and 11C-l-(−)-cocaine (bottom row, from 0–54 min) in same animal. 11C distribution is widespread over cortical and subcortical brain regions for 11C-d-methamphetamine but is highly localized in striatum for 11C-(−)-cocaine. Images are coregistered to MRI atlas (20).

  • FIGURE 2. 
    FIGURE 2. 

    Time–activity curves for cortical and subcortical brain regions for 11C-d-methamphetamine (A) and 11C-l-methamphetamine (B) in same baboon (BEJ285dy1 and BEJ285dy2 refer to study number). Brain kinetics are similar for different brain regions.

  • FIGURE 3. 
    FIGURE 3. 

    Comparison of 11C-d-methamphetamine (A) and 11C-l-methamphetamine (B) distribution in peripheral organs in baboon (BEJ288dy1 and BEJ288dy2 refer to study number). 11C distribution is similar for the 2 enantiomers.

  • FIGURE 4. 
    FIGURE 4. 

    Time–activity curves for 11C-d-methamphetamine (A) and 11C-(−)-cocaine (B) in cerebellum and striatum in same baboon (BEJ298dy1 and BEJ298dy2 refer to study number). Clearance of 11C-d-methamphetamine is lower and slower than that of 11C-(−)-cocaine.

  • FIGURE 5. 
    FIGURE 5. 

    Comparison of distribution and clearance of 11C-d-methamphetamine (A) and 11C-(−)-cocaine (B) in peripheral organs in same baboon (BEJ303dy1 and BEJ303dy2 refer to study number). Both compounds show similar distribution and kinetics in heart, lungs, and liver, but d-methamphetamine has much greater uptake and slower clearance in kidneys and higher uptake in pancreas than does 11C-(−)-cocaine.

Tables

  • TABLE 1

    Summary of Baboon PET Studies

    Study no.Baboon's nameRadiotracerLocationDrug treatment
    d vs. l
     BEJ284dy1,2Spiceyl (run 1); d (run 2)BrainNone
     BEJ285dy1,2Friendlyd (run 1); l (run 2)BrainNone
     BEJ307dy1,2Daisyd (run 1); l (run 2)BrainNone
     BEJ288dy1,2Daisyd (run 1); l (run 2)TorsoNone
     BEJ290dy1,2Chloel (run 1); d (run 2)TorsoNone
    d vs. drug treatment
     BEJ280dy1,2Daisyd (run 1); d (run 2)BrainNone
     BEJ287dy1,2Missyd (run 1); d (run 2)BrainBaseline; d-methamphetamine, 0.2 mg/kg intravenously, 5 min prior
     BEJ291dy1,2Pearld (run 1); d (run 2)BrainBaseline; methylphenidate, 0.5 mg/kg intravenously, 10 min prior
     BEJ329dy1,2Spiceyd (run 1); d (run 2)BrainBaseline; tetrabenazine; 4 mg/kg intravenously, 60 min prior
    d vs. 11C-(−)-cocaine
     BEJ303dy1,2Friendlyd (run 1); cocaine (run 2)TorsoNone
     BEJ298dy1,2MissyCocaine (run 1); d (run 2)BrainNone

    • d = 11C-d-methamphetamine; l = 1C-l-methamphetamine.

  • TABLE 2

    Comparison of Data for Striatum and Cerebellum

    Parameter11C-d-methamphetamine11C-l-methamphetamine
    % dose/cm3 (peak)
     Striatum0.033 ± 0.0080.036 ± 0.003
     Cerebellum0.034 ± 0.010.034 ± 0.004
    Peak time (min)
     Striatum7.2 ± 2.37.5 ± 2.6
     Cerebellum4.5 ± 4.54.5 ± 1.5
    Clearance half-time from peak (min)
     Striatum80.3 ± 18.698.5 ± 22.3
     Cerebellum59.3 ± 18.367.5 ± 12.3
    DVR (Striatum:cerebellum)1.22 ± 0.041.22 ± 0.027
    Plasma integral for total 11C at 60 min*2,411 ± 399 (1,348 ± 33)1,833 ± 203 (1,351 ± 51)

    • ↵* There was a trend toward greater 11C in plasma at 60 min for d-enantiomer (P < 0.08). Data in parentheses are fraction of 11C as methamphetamine (mean ± SD, n = 3).

  • TABLE 3

    Comparison of Fraction of Total 11C in Plasma That Is Present as Parent Radiotracer at Different Times After Injection

    Time (min)11C-d-methamphetamine (n = 9)11C-l-methamphetamine (n = 3)P
    293 ± 2.495 ± 2NS
    583 ± 589 ± 2.30.06
    1069.9 ± 6.882.3 ± 3.50.01
    2053.4 ± 8.572 ± 6.20.006
    3044.4 ± 8.567 ± 9.60.003
    6032.3 ± 7.758.7 ± 13.050.002
    9026.9 ± 6.449 ± 170.01

    • NS = not statistically significant.

  • TABLE 4

    Comparison of DVRs at Baseline and After Drug Treatment for 11C-d-Methamphetamine

    DrugDVR (baseline)DVR (after treatment)% Change
    Control1.211.28+5
    d-Methamphetamine1.191.16−2
    Methylphenidate1.281.19−7
    Tetrabenazine1.181.24+5
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