Parametric mapping of [18F]FPCIT binding in early stage Parkinson's disease: A PET study

We have shown that fluorinated N‐3‐fluoropropyl‐2‐beta‐carboxymethoxy‐3‐beta‐(4‐iodophenyl) nortropane ([18F]FPCIT) and PET offer a valuable means of quantifying regional abnormality in dopamine transporter (DAT) imaging associated with Parkinson's disease (PD). The objective of this study was to delineate the topographic distribution of DAT binding in early stage idiopathic PD using statistical parametric analysis of [18F]FPCIT PET data. We performed dynamic PET studies in 15 hemi‐parkinsonian (Hoehn & Yahr I) patients and 10 age‐matched normal volunteers over 100 min and calculated images of [18F]FPCIT binding ratios on a pixel‐by‐pixel basis. Statistical parametric mapping (SPM) was then used to localize binding reductions in PD and to compute the absolute change relative to normal. [18F]FPCIT binding decreased significantly in the contralateral posterior putamen of the PD group (P < 0.001, corrected). A significant reduction was also seen in the ipsilateral putamen, which was smaller in extent but localized more posteriorly. A quantitative comparison of DAT binding in the two clusters showed that the onset of motor symptoms in PD was associated with an approximate 70% loss relative to the normal mean in the contralateral posterior putamen. These results suggest that SPM analysis of [18F]FPCIT PET data can be used to quantify and map abnormalities in DAT activity within the human striatum. This method provides a useful tool to track the onset and progression of PD at its earliest stages. Synapse 45:125–133, 2002. © 2002 Wiley‐Liss, Inc.

[1]  S J Kish,et al.  [11C]RTI‐32 PET studies of the dopamine transporter in early dopa‐naive Parkinson's disease , 1997, Neurology.

[2]  C. Patlak,et al.  Combined FDOPA and 3OMFD PET studies in Parkinson's disease. , 1996, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[3]  Robert B. Innis,et al.  Iodine-123-β-CIT and Iodine-123-FPCIT SPECT Measurement of Dopamine Transporters in Healthy Subjects and Parkinson's Patients , 1998 .

[4]  J. Holden,et al.  Reproducibility and discriminating ability of fluorine-18-6-fluoro-L-Dopa PET in Parkinson's disease. , 1996, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[5]  C Trenkwalder,et al.  Striatal dopamine transporter binding assessed by [I-123]IPT and single photon emission computed tomography in patients with early Parkinson's disease: implications for a preclinical diagnosis. , 2000, Archives of neurology.

[6]  V. Sossi,et al.  In vivo positron emission tomographic evidence for compensatory changes in presynaptic dopaminergic nerve terminals in Parkinson's disease , 2000, Annals of neurology.

[7]  P. David Mozley,et al.  Logistic discriminant parametric mapping: a novel method for the pixel-based differential diagnosis of Parkinson’s disease , 1999, European Journal of Nuclear Medicine.

[8]  N. Volkow,et al.  Dopamine transporters decrease with age. , 1996, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[9]  Alan C. Evans,et al.  Regional striatal DOPA transport and decarboxylase activity in Parkinson's disease. , 1995, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[10]  Jan Booij,et al.  Iodine-123-N-ω-Fluoropropyl-2β-Carbomethoxy-3β-(4-Iodophenyl)Tropane SPECT in Healthy Controls and Early-Stage, Drug-Naive Parkinson's Disease , 1998 .

[11]  J. Seibyl,et al.  Effect of treatment with L‐dopa/carbidopa or L‐selegiline on striatal dopamine transporter SPECT imaging with [123I]β‐CIT , 1999, Movement disorders : official journal of the Movement Disorder Society.

[12]  Karl J. Friston,et al.  Frontal, midbrain and striatal dopaminergic function in early and advanced Parkinson's disease A 3D [(18)F]dopa-PET study. , 1999, Brain : a journal of neurology.

[13]  N. Alpert,et al.  Rapid detection of Parkinson's disease by SPECT with altropane: A selective ligand for dopamine transporters , 1998, Synapse.

[14]  T G Turkington,et al.  Performance characteristics of a whole-body PET scanner. , 1994, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[15]  J. Hietala,et al.  [18F]CFT ([18F]WIN 35,428), a radioligand to study the dopamine transporter with PET: Characterization in human subjects , 1998, Synapse.

[16]  J. Zubieta,et al.  PET imaging of the dopamine transporter in progressive supranuclear palsy and Parkinson’s disease , 1999, Neurology.

[17]  A. Lees,et al.  Ageing and Parkinson's disease: substantia nigra regional selectivity. , 1991, Brain : a journal of neurology.

[18]  V. Dhawan,et al.  Dopamine transporter imaging with fluorine-18-FPCIT and PET. , 1998, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[19]  J D Speelman,et al.  One-day protocol for imaging of the nigrostriatal dopaminergic pathway in Parkinson's disease by [123I]FPCIT SPECT. , 1999, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[20]  T. Autti,et al.  Decreased striatal dopamine transporter density in JNCL patients with parkinsonian symptoms , 2000, Neurology.

[21]  D J Brooks,et al.  Regional changes in [18F]dopa metabolism in the striatum in Parkinson's disease. , 1996, Brain : a journal of neurology.

[22]  D J Wyper,et al.  Correlation of Parkinson's disease severity and duration with 123I‐FP‐CIT SPECT striatal uptake , 2000, Movement disorders : official journal of the Movement Disorder Society.

[23]  M. Ichise,et al.  SPECT imaging of pre- and postsynaptic dopaminergic alterations in l-dopa–untreated PD , 1999, Neurology.

[24]  A. Alavi,et al.  Binding of [99mTc]TRODAT-1 to dopamine transporters in patients with Parkinson's disease and in healthy volunteers. , 2000, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[25]  T Jones,et al.  The nigrostriatal dopaminergic system assessed in vivo by positron emission tomography in healthy volunteer subjects and patients with Parkinson's disease. , 1990, Archives of neurology.

[26]  J. Haycock,et al.  Striatal 3,4‐dihydroxyphenylalanine decarboxylase in aging: Disparity between postmortem and positron emission tomography studies? , 1995, Annals of neurology.

[27]  N. Volkow,et al.  Comparison of two pet radioligands for imaging extrastriatal dopamine transporters in human brain. , 1995, Life sciences.

[28]  S. E. Kim,et al.  SPECT measurement of iodine-123-beta-CIT binding to dopamine and serotonin transporters in Parkinson's disease: correlation with symptom severity. , 1999, Neurological research.

[29]  Christer Halldin,et al.  [18F]β-CIT-FP is superior to [11C]β-CIT-FP for quantitation of the dopamine transporter , 1997 .

[30]  V. Dhawan,et al.  Radiosynthesis of [18F] N-3-fluoropropyl-2-β-carbomethoxy-3-β-(4-iodophenyl) nortropane and the first human study with positron emission tomography , 1996 .

[31]  T. Ishikawa,et al.  Comparative nigrostriatal dopaminergic imaging with iodine-123-beta CIT-FP/SPECT and fluorine-18-FDOPA/PET. , 1996, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[32]  J. C. Stoof,et al.  Drug-naive patients with Parkinson’s disease in Hoehn and Yahr stages I and II show a bilateral decrease in striatal dopamine transporters as revealed by [123I]β-CIT SPECT , 1997, Journal of Neurology.