The nigrostriatal dopaminergic system assessed in vivo by positron emission tomography in healthy volunteer subjects and patients with Parkinson's disease
K. L. Leenders, E. P. Salmon, P. Tyrrell, D. Perani, D. J. Brooks, H. Sager, T. Jones, C. D. Marsden and R. S. Frackowiak
MRC Cyclotron Unit, Hammersmith Hospital, London, England.
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.
6-L-18F-Fluorodihydroxyphenylalanine PET in Neuroendocrine Tumors: Basic Aspects and Emerging Clinical Applications
Jager et al.
JNM 2008;49:573-586.
ABSTRACT
| FULL TEXT
18F-DOPA PET and PET/CT
Nanni et al.
JNM 2007;48:1577-1579.
FULL TEXT
Pharmacological Characterization of (E)-N-(4-Fluorobut-2-enyl)-2beta-carbomethoxy-3beta-(4'-tolyl)nortropane (LBT-999) as a Highly Promising Fluorinated Ligand for the Dopamine Transporter
Chalon et al.
J. Pharmacol. Exp. Ther. 2006;317:147-152.
ABSTRACT
| FULL TEXT
The role of radiotracer imaging in Parkinson disease
Ravina et al.
Neurology 2005;64:208-215.
ABSTRACT
| FULL TEXT
(123I) {beta}-CIT and Single-Photon Emission Computed Tomographic Imaging vs Clinical Evaluation in Parkinsonian Syndrome: Unmasking an Early Diagnosis
Jennings et al.
Arch Neurol 2004;61:1224-1229.
ABSTRACT
| FULL TEXT
The L-dopa response in vascular parkinsonism
Zijlmans et al.
J. Neurol. Neurosurg. Psychiatry 2004;75:545-547.
ABSTRACT
| FULL TEXT
Parkinson's disease: piecing together a genetic jigsaw
Dekker et al.
Brain 2003;126:1722-1733.
ABSTRACT
| FULL TEXT
Quantification of Dopamine Transporter by 123I-PE2I SPECT and the Noninvasive Logan Graphical Method in Parkinson's Disease
Prunier et al.
JNM 2003;44:663-670.
ABSTRACT
| FULL TEXT
Slowing Parkinson's disease progression: Recent dopamine agonist trials
Ahlskog
Neurology 2003;60:381-389.
ABSTRACT
| FULL TEXT
Anticholinergic drugs: response of parkinsonism not responsive to levodopa
Yamada et al.
J. Neurol. Neurosurg. Psychiatry 2002;72:111-113.
ABSTRACT
| FULL TEXT
The nigrostriatal dopaminergic system in familial early onset parkinsonism with parkin mutations
Portman et al.
Neurology 2001;56:1759-1762.
ABSTRACT
| FULL TEXT
An algorithm (decision tree) for the management of Parkinson's disease (2001):: Treatment
Olanow et al.
Neurology 2001;56:S1-S88.
FULL TEXT
Response to Levodopa Treatment in Dopa-Responsive Dystonia
Nutt and Nygaard
Arch Neurol 2001;58:905-910.
ABSTRACT
| FULL TEXT
Glial Cell Line-Derived Neurotrophic Factor Is Essential for Postnatal Survival of Midbrain Dopamine Neurons
Granholm et al.
J. Neurosci. 2000;20:3182-3190.
ABSTRACT
| FULL TEXT
Usefulness of a dopamine transporter PET ligand [18F]beta -CFT in assessing disability in Parkinson's disease
Rinne et al.
J. Neurol. Neurosurg. Psychiatry 1999;67:737-741.
ABSTRACT
| FULL TEXT
Dopaminergic Dysfunction in Parkinsonism: New Lessons from Imaging
Marek
Neuroscientist 1999;5:333-340.
ABSTRACT
Vulnerability of the nigrostriatal system as detected by transcranial ultrasound
Berg et al.
Neurology 1999;53:1026-1026.
ABSTRACT
| FULL TEXT
Presynaptic Dopaminergic Deficits in Lesch-Nyhan Disease
Ernst et al.
NEJM 1996;334:1568-1572.
ABSTRACT
| FULL TEXT
