SPECT in ParkinsonismDr Gulab Soni

SPECT-Principle• Image and quantify a physiological function or molecular target of

interest (e.g., blood flow, metabolism, receptor binding) in vivo by noninvasively assessing the spatial and temporal distribution of the radiation emitted by an intravenously injected target-specific probe (radiotracer)• Molecular imaging techniques

Single-Photon Emission Computed Tomography(SPECT)• SPECT employs gamma-emitting radionuclides that decay by emitting

a single gamma ray• Spatial resolution of modern SPECT is only about 7 to 10 mm• Single SPECT acquisition usually takes 20 to 30 minutes• Radionuclides for SPECT-1) Technetium-99m (99mTc; half-life = 6.02 hours) 2) Iodine-123 (123I; half-life = 13.2 hours)

Clinical application of SPECT• Diagnostic utility• Prognostic utility-disease progression

SPECT in Parkinsonism Imaging of the dopaminergic system Perfusion imaging

Imaging of the dopaminergic system 1) Dopamine synthesis2) Dopamine storage in synaptic vesicles3) Dopamine transporters4) Dopamine receptors

Radiotracer used for SPECT in ParkinsonismTargeting Tracer

Dopamine reuptake(dopamine transport)

123I-β-CIT,123I-FP-β-CIT,123I-IPT,123I-Altropane,123I-β-PE2I99Tcm-TRODAT-1

D2 dopamine receptor 123I-Iodospiperone,123I-Iodobenzamide (123I-IBZM),123I-Iodolisuride, 123I-IBF

Dopamine transporters• Dopamine transporters (DAT) are located in the presynaptic

dopaminergic nerve terminal. • Dopamine reuptake through the DAT is the primary mechanism of

dopamine removal from the region of the synaptic cleft • DAT-specific tracers used for SPECT imaging are cocaine analogue and

ability to assess decreased DAT density, which may precede clinical symptoms in PD

Dopamine transporters• The reduction is typically more severe in the striatum contralateral to

the earliest and most affected body side • Striatal DAT levels, particularly in the putamen, correlate with disease

severity and decrease with PD progression

Dopamine receptors• SPECT studies with [123I]IBJM showed that striatal dopamine D2

binding to the postsynaptic dopaminergic receptors was either normal or increased in PD patients• This increase has been interpreted as a compensatory reaction to the

reduction of striatal dopaminergic terminals • D2 receptor upregulation is most evident at early stages and

contralateral to the clinically most affected side and is usually the site of onset in PD.

Dopamine receptors• D2 receptor imaging is widely used for the differential diagnosis of

parkinsonism, since uptake is typically normal or increased in patients with PD, whereas patients with other forms of parkinsonism, such as multiple system atrophy and progressive supranuclear palsy show reduced tracer uptake• Chronic pharmacologic treatment may reduce D2 receptor availability,

probably due to downregulation• Shows 59 to 80% sensitivity and 46 to 50% specificity in differentiating

PD from other atypical PD

Clinical indications for DaT-SPECT imaging Indications1) Only 1 of 3 cardinal clinical signs with or without asymmetry2) Poor response to L-dopa3) Lack of disease progression(Cardinal signs are resting tremor, rigidity, and bradykinesia and postural instability)

DAT-SPECTDifferentiating between Parkinson’s Essential tremorDystonic tremorDrug-induced parkinsonismPsychogenic parkinsonismVascular parkinsonism

DAT-SPECT • Specificity-100% • Sensitivity : 38% to 100%• 15% of patients diagnosed as having PD had normal DaT-SPECT study

findings classified as “scans without evidence of dopaminergic deficit” (SWEDD)

DAT-SPECT• Because most dopaminergic

transmission occurs in the striatum, this area will show the maximum uptake of DaT radiotracers, with minimal background activity in the remainder of the brain.• In scans with normal findings, the

striata appear as symmetric “comma” shapes• Any asymmetry or distortion of this

shape, in the absence of patient motion, implies an abnormal scan finding.

Brain perfusion imaging

Perfusion-SPECT

Brain perfusion SPECT• Used for measuring regional cerebral blood flow (rCBF) are lipophilic

agents which are transported from the vascular compartment to the normal brain tissue compartment by diffusion and are distributed proportionally to regional tissue blood flow• Tc-99m hexamethyl-propylene amine oxime (Tc-99m HMPAO) • Tc-99m ethyl cysteinate dimer (Tc-99m ECD)

Brain perfusion SPECT• Approximately 10% of Parkinson’s disease patients develop dementia,

with parietal, temporal, and occipital lobe hypoperfusion seen on brain SPECT studies. • Demented Parkinson’s disease patients and AD patients share a

common pattern of marked posterior hypoperfusion. However, the defects are more prominent and extensive in AD

Spampinato U, Habert MO, Mas JL, et al. (99mTc)-HM-PAO SPECT and cognitive impairment in Parkinson’s disease: a comparison with dementia of the Alzheimer type. J Neurol Neurosurg Psychiatry. 1991;54:787–792

Summary of nuclear imaging in

Parkinsonism

PET vs SPECT

Positron emission tomography (PET)• Very expensive• Uses positron emitting

radioisotope (tracer)a) 18F• Better contrast and spatial

resolution• Short half life of tracer

Single-photon emission computed tomography (SPECT)• Lower cost• Uses gamma emitting

radioisotope (tracer)a) Technetium-99mb) Iodine-123• Less contrast and spatial

resolution • Long half life of tracer

PET & SPECT in Parkinsonism

DAT-SPECT

FDG-PET

THANK-U