Idiopathic Parkinson's Progression and Dopamine Transporter SPECT

Background: Idiopathic Parkinson's disease (PD) is a neurodegenerative disorder involving
loss of dopaminergic neurons in the substantia nigra and subsequent dysfunction in the
striatum. The diagnosis of PD remains a clinical diagnosis based on patient history and
physical exam findings. In 2011 the FDA approved the use of DaTscanTM Ioflupane I123, a
radiopharmaceutical to be used as an adjunct diagnostic tool in combination with single
photon emission computed tomography (SPECT) to evaluate striatal dopamine transporter (DAT)
distribution in patients with an unclear diagnosis of parkinsonism vs essential tremor (Bajaj
et al., 2013). Because the loss of DAT binding in the striatum reflects the loss of
dopaminergic neurons in parkinsonism, DAT SPECT is considered a highly sensitive test for
these disorders (Ba and Martin, 2015). The major clinical uncertainty with DAT SPECT imaging
is whether or not quantitative analysis can be utilized to determine progressive degeneration
over time and serve as a quantitative biomarker for changes in striatal dopaminergic
integrity in correlation with clinical worsening in patients with idiopathic PD. In 3 small
studies using two other ligands, 18F-dopa and I123β-CIT, striatal uptake declined annually by
12.5-13%, and 2.4% - 7.1%, respectively (Morrish et al., 1996; Nurmi et al., 2000; Pirker et
al., 2012). Current analytical methodologies have focused on establishing differences between
the PD and control groups, but have not explored the technology for tracking disease
progression with Ioflupane I123, using the patient as their own control. The goal of this
proposed study is to evaluate the validity of quantitative measurements in DAT SPECT scans in
determining disease progression in subjects with idiopathic PD. Data from this pilot study
would contribute significantly to future applications for investigating translational
research strategies to restore dopaminergic cell function in PD. More specifically, the
ability of autologous peripheral nerve grafts, acting as a source of neuroregenerative growth
factors, is being investigated in PD subjects undergoing deep brain stimulation (Craig van
Horne, PI). As there are no current biomarkers for PD progression, it is critical to evaluate
the potential for DAT SPECT to serve as an analytical tool for the quantification of
dopaminergic functional integrity. This study is designed to test the ability of DAT SPECT to
be used as an effective methodology for tracking disease progression where patients serve as
their own control.

Objectives: The specific aim is to evaluate the ability of DAT SPECT quantification to track
disease progression in subjects with idiopathic Parkinson's disease by comparing baseline
scans to those obtained 12 months later. The quantified DAT SPECT data will be clinically
correlated to the Movement Disorder Society Unified Parkinson's Disease Rating Scale
(MDS-UPDRS) motor scores and Hoehn and Yahr stage obtained at baseline and at 12 months.

Study Design: This will be an initial phase of a prospective study evaluating DAT SPECT
quantification in subjects with idiopathic Parkinson's disease. The clinical severity of PD
will be measured by MDS-UPDRS motor scores and the Hoehn and Yahr scale. Data will be
acquired at baseline, and 12 months. The subject will serve as their own control.

Inclusion Criteria:

- Between the ages of 40-75

- Able to give informed consent

- Show a positive response to carbidopa/levodopa

- Hoehn and Yahr score 1-3

Exclusion Criteria:

- Under the age of 40 or over the age of 75

- Unable to give informed consent

- Nonresponsive to carbidopa/levodopa

- Hoehn and Yahr score 4-5

- Unable to discontinue medications which might interfere with DaTscan TM imaging

- Inability to lie still for 30-45 minutes during CT-SPECT imaging

- Pregnancy or Nursing

- Severe kidney function impairment

- Unable to tolerate iodine containing products

- Patients with deep brain stimulation (DBS) or a history of any other brain surgery