Four year Longitudinal Assessment of Scintigraphic Imaging Biomarkers in a Progressing Parkinson Disease Cohort

Objectives: Several imaging and non-imaging measures have been proposed as putative Parkinson Disease (PD) progression biomarkers to provide more objective measure of disease status in order to improve clinical assessment of disease modifying therapies. The Parkinson Progression Marker Initiative (PPMI) study is an international, multicenter longitudinal evaluation of biomarkers in a progressing early Parkinson's disease cohort. The aims of this study are to evaluate within subject changes in dopamine (DAT) and vesicular (VMAT2) transporters using 123-I Ioflupane SPECT and 18-F AV-133 PET, respectively, in PD participants studied over four years

Methods: In an ongoing study 154 de novo PD subjects completed baseline, 2yr, 3yr, and 4yr clinical and ¹²³I-Ioflupane/SPECT evaluations. A substudy of 17 of these subjects also had baseline, Y1, and Y2 18-F AV-133 PET. Changes in specific binding ratio (SBR) between baseline and 2-yr, 3-yr, and 4-yr scans were calculated for ipsilateral and contralateral striatum as well as striatal subregions. Rates of signal change were compared with changes in clinical ratings.

Results: Annualized rates of % change in DAT composite SBR are 10-12% in the first year with lower reductions in SBR by year 4, for an average annualized change of 7%. VMAT2 show 10-12% reductions in Y1 and 24.5% by Y2, with lower variance than DAT. When DAT data were parsed into subregions, in Y 1 there is a progressive increase in the rate of change in SBR in the ipsilateral striatum in an anterior to posterior pattern moving from caudate to anterior putamen to posterior putamen. This pattern is not seen on the contralateral side. By Y4 the rates of SBR change equalizes across subregions, without evidence of floor efffects due to low signal:noise.

Conclusion: The use of 123-I ioflupane SPECT or 18-F AV-133 PET as a biomarker of PD progression is feasible from the perspective of the size of signal change in an early PD cohort studied over 2-4 years with the better regions for tracking early change the composite SBR or caudate. Research Support: M. J. Fox Foundation for Parkinson's Research