Clinical Utility of DAT Imaging in Diagnosis of Parkinson syndrome

123-I ß-CIT (Dopascan)

Cocaine 123-I ß-CIT

• 123-Iodine ß-CIT is a phenyltropane analog of cocaineradiopharmaceutical for imaging dopamine transporters in brain

123-I FP-CIT

123-I ß-CIT State and Trait Biomarker for PD

Nigral Dopamine loss -

Face validity

(> 4000 scans in > 30 clinical imaging studies)

Reduction in early PD

50% Put

Reduction Put>Caud

Yes

Reduction asymmetric

Yes

Correlation with severity

Yes

(UPDRS)

Reduction in Pre-diagnostic Yes

Monitor PD progression

Yes

Time

Neu

ron

Func

tion

Clin

ical

Rat

ings

Pre-diagnostic

Symptomatic

Diagnosis

Natural History of PD No Treatment

Symptom Threshold

50-60% loss of contra put

DAT Imaging for diagnosis of Parkinson syndrome: Suspects and SWEDD

• Patients with Suspected PS -

can DAT imaging improve diagnostic accuracy?

• Subjects enrolled in clinical trials with Scans without evidence of dopaminergic deficit (SWEDD) –

can DAT imaging

identify subjects who do not have PS.

Unsure about a Parkinsonian diagnosis??

Consider a referral to the Query-PD study and participate in the development of a diagnostic tool for PD

Methods• Patients with suspected PS, referred by

community neurologists for imaging.• Referring neurologist provided:

– ‘best guess’ diagnosis– Certainty of diagnosis – Info regarding specific PD symptoms (rest

tremor, bradykinesia, rigidity, etc)– Response to dopaminergic medications

• Baseline: MDE examination• Baseline: [123I]β-CIT/SPECT

– Visual and quantitative outcome compared with healthy database (n=100)

• 3 month f/u: clinical dx (blind to imaging data) • 12 month f/u: clinical dx (blind to imaging data)

determined ‘Gold standard’ diagnosis

Demographics/Baseline Data

Community Neurologists (n=37)Patients enrolled (n=137) Patients completing final clinical visit (n=131)

Age 62.3 yrs (range 30-92)Gender 54% male, 46% femaleSx duration 2.1 yrs

Baseline imaging and clinical assessment of this population of suspected PS compared to independent MDE 12 mo dx -

‘Gold Standard’

Final Clinical Diagnosis PS No PS Sensitivity SpecificityArea under the curve

Enolling MDE baselinePS 57 32 0.97 0.55 0.76

No PS 2 39Independent MDE baseline

PS 45 9 0.76 0.88 0.82No PS 14 63

Quantitative ImagingPS 52 8 0.88 0.89 0.89

No PS 7 64

Referral neurologist identified population of suspected PS36 neurologist referred 137 subjects

59 (43 %) PS, 68 (57%)not PSBased on independent MDE 12 mo dx -

‘Gold Standard’

QUERY-PS STUDY

Referral neurologist treatment response to imaging data

QUERY-PS STUDY

SWEDD (Scans Without Evidence of Dopaminergic Deficit) in PD Trials

Study

Stage –PD

Dur DX at

% SWEDD

Baseline(mo)

Elldopa-CIT Denovo

6

21/142 (14%)

PRECEPT

Denovo

8

91/799 (12%)

REAL-PET

Denovo

9

21/186 (11%)

Calm-CIT

Start of 18 3/82 (4%)DA Rx

GPI1485

Treated

23

3/212 (1.4%)

Stable responder

Scans without evidence of deficit (SWEDD)

Scans <75% Age adjustedHealthy subjects

SWEDD

DAT Deficit

PRECEPT study - FOLLOWUP IMAGING AND CLINICAL OUTCOMES BY SWEDD STATUS

AT BASELINE

Mean (SD) for Change in [123I] ß-CIT and UPDRS, Percent (CI) for need for DA treatment. * indicates p < 0.01

DAT imaging in diagnosis of PS

•

Need for additional diagnostic tools for community neurologists for difficult to diagnose subjects with suspected PS –

DAT imaging is a

useful tool for these patients.

•

DAT imaging can identify subjects without PS even among subjects enrolled into PD clinical trials –

DAT imaging is a useful tool to identify patients who do not have PS.