Analysis of four dopaminergic tracers kinetics using two different tissue input function methods.
The integrity of the dopaminergic system can be studied using positron emission tomography. The presynaptic tracers [11C]-methylphenidate and [11C]dihydrotetrabenazine (DTBZ) are used to investigate the dopamine transporter availability, the dopamine vesicular transporter integrity; the postsynaptic tracers [11C]-raclopride and [11C]-Schering 23990 (SCH) are used to probe the D2 and D1 receptors. These are reversible tracers, where the binding potential (BP) = Bmax/Kd often is used to quantify the amount of their specific binding to the sites of interest. The simplified tissue input methods to calculate BP are attractive, since they do not require a blood input function. The suitability and performance of two such methods were evaluated: the Logan graphical tissue method, and the Lammertsma reference tissue method (RTM). The BP estimates obtained with the two methods were nearly identical in most cases, with similar reliability and reproducibility indicating that all four tracers satisfy the assumptions required by each method. The correlations among the fitted parameters obtained from the RTM were estimated and were found not to introduce noticeable bias in the RTM BP and R1 estimates. R1 showed low intersubject and intrasubject variability. The k2 estimate showed good reliability for SCH with cerebellar input function and DTBZ with occipital input function.
Sossi
V
V
UBC/TRIUMF, Vancouver, BC, Canada.
Holden
J E
JE
Chan
G
G
Krzywinski
M
M
Stoessl
A J
AJ
Ruth
T J
TJ
D000328:Adult; D000368:Aged; D001552:Benzazepines / Q000378:metabolism / Q000493:pharmacokinetics; D002352:Carrier Proteins / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000378:metabolism / Q000493:pharmacokinetics*; D065127:Dopamine D2 Receptor Antagonists; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors / Q000378:metabolism / Q000493:pharmacokinetics*; D006801:Humans; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors; D026901:Membrane Transport Proteins; D008774:Methylphenidate / Q000378:metabolism / Q000493:pharmacokinetics*; D008875:Middle Aged; D008954:Models, Biological; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D020891:Raclopride / Q000378:metabolism / Q000493:pharmacokinetics*; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D013747:Tetrabenazine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D050492:Vesicular Biogenic Amine Transport Proteins
D001552:Benzazepines; D002352:Carrier Proteins; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D017447:Receptors, Dopamine D1; D050492:Vesicular Biogenic Amine Transport Proteins; D008774:Methylphenidate; C032811:dihydrotetrabenazine; D020891:Raclopride; D004298:Dopamine; D013747:Tetrabenazine