The nigrostriatal dopaminergic system assessed in vivo by positron emission tomography in healthy volunteer subjects and patients with Parkinson's disease.
A group of healthy control subjects and patients with Parkinson's disease were investigated using positron emission tomography and two tracers as indicators of different specific properties of the presynaptic dopaminergic system in caudate nucleus and putamen. The first tracer, 6-L-(18F)-fluorodopa, was used as an analog of levodopa to assess its regional brain uptake, conversion into, and retention as dopamine and further metabolites. The second tracer, (11C)-nomifensine was employed as an indicator of striatal monaminergic reuptake sites that are principally dopaminergic. We have used this tracer to assess dopaminergic nerve terminal density. In patients with Parkinson's disease, striatal uptake of both tracers was decreased, putamen being significantly more affected than caudate. Side-to-side differences of uptake in putamen, but not caudate, correlated with corresponding left-right differences of scored clinical motor performance. Both 6-L(18F)-fluorodopa and (11C)-nomifensine tracer uptake in putamen was decreased on average to 40% of normal values, suggesting that a substantial part of the cellular elements of the dopaminergic nigrostriatal system is still intact in living parkinsonian patients. This is in contrast to the generally extreme depletion of endogenous dopamine in the putamen of patients found at postmortem. Our results lend support to the search for drug treatments that protect against further nigrostriatal cell loss and that could be exhibited as soon as the disease manifests clinically. If successful, a sufficient striatal nerve terminal pool would remain so that the effectiveness of levodopa as a dopamine repletor could persist.
Leenders
K L
KL
MRC Cyclotron Unit, Hammersmith Hospital, London, England.
Salmon
E P
EP
Tyrrell
P
P
Perani
D
D
Brooks
D J
DJ
Sager
H
H
Jones
T
T
Marsden
C D
CD
Frackowiak
R S
RS
D000368:Aged; D002250:Carbon Radioisotopes; D002421:Caudate Nucleus / Q000000981:diagnostic imaging* / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives; D004298:Dopamine / Q000378:metabolism*; D005462:Fluorine Radioisotopes; D006801:Humans; D008875:Middle Aged; D009627:Nomifensine / Q000493:pharmacokinetics; D010300:Parkinson Disease / Q000000981:diagnostic imaging* / Q000378:metabolism; D011699:Putamen / Q000000981:diagnostic imaging* / Q000378:metabolism; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D005462:Fluorine Radioisotopes; D009627:Nomifensine; C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; D004298:Dopamine