The dopamine transporter is increasingly recognized as a window on the status of dopamine neurons Dopamine transporter levels decline in tandem with the loss of dopamine in Parkinson's disease and in experimentally produced parkinsonism The dopamine transporter is also a principal target of Ritalin , Zyban and cocaine in brain Although it is feasible to accurately measure the density of the transporter in post-mortem tissue, measures of transporter density in living brain by PET or SPECT imaging are more challenging With PET imaging in non-human primate brain, we measured transporter levels using a technique of three injections of [11C]CFT (WIN 35,428) followed by non-linear least-squares (NLSQ) fitting of all the dynamic data simultaneously The resulting data yielded a value for B'max which does not correspond closely to B'max/Kd The advantages of the three-injection model is the feasibility of measuring B'max and Kd (Koff/Kon) separately It is inadvisabl e to use B'max/Kd or distribution volume ratio (DVR) in all circumstances as an indicator of B'max as the underlying assumption for generating binding potential is the constancy of Kd For receptor imaging, agonist drugs can convert receptors from high to low affinity, thereby reducing the apparent Kd for PET imaging agents that are either agonists or partial agonists Kd may also differ as a function of other factors, including age, pathological states, mutations in receptors, or modifications of the membrane matrix of protein targets If feasible, it seems imprudent to sacrifice the possibility of obtaining accurate data with measures of Kd and B'max

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000168-39
Application #
6313077
Study Section
Project Start
1978-06-01
Project End
2003-04-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
39
Fiscal Year
2000
Total Cost
$13,085
Indirect Cost
Name
Harvard University
Department
Type
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
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