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Efficacy of SPECT in Differentiating Dementia with Lewy Bodies
Table1: Radioactive Ligands Used with Single Photon Emission Computed Tomography
Function Ligand – Ligand – Quantity Time to Scan
Common Abbreviation Full Chemical Name
Dopamine imaging
123
I-β-CIT [
123
I]2β‚-carboxymethoxy-3β‚-(4- iodophenyl) tropane 145–185MBq 18–24 hours
123
I-FP-CIT [
123
I]N- (3-fluoropropyl)-2β‚-carbometoxy-3β‚-(4-iodophenyl) nortropane 185MBq 3–6 hours
123
I-IBZM [
123
I]iodobenzamide 185MBq 1.5–2 hours
Perfusion
99m
Tc-HMPAO Technetium-99m-hexamethylpropylene amine oxime 500MBq 10 minutes
99m
Tc-ECD Technetium-99m-ethyl cysteinate dimer 555MBq 15 minutes
123
I-IMP N-isopropyl-p-[123I]iodoamphetamine 222MBq 15 minutes
Myocardial scintigraphy
123
I-MIBG [
123
I]metaiodobenzylguanidine 111MBq 15 minutes
Cholinergic imaging
123
I-5IA-85380 (nicotinic) [
123
I]-5-Iodo-3-[2(S)-2-azetidinylmethoxy] pyridine 185MBq 2 hours
123
I-QNB (muscarinic) [
123
I]-iodo-quinuclidinyl-benzilate 185MBq 5 hours
for the diagnosis of DLB,
1
which now include “low dopamine Figure 1: FP-CIT Labels Dopamine Transporter in
transporter uptake in the basal ganglia demonstrated by SPECT
Nigrostriatal Nerve Terminals in the Striatum
imaging” as a “suggestive feature” for DLB.
A B
Efficacy of Pre-synaptic Dopamine Imaging
Initial semi-quantitative studies with [
123
I]-2β-carbomethoxy-3β-(4-
iodophenyl) tropane (b-CIT) and [
123
I]-N-(3-fluoropropyl)-2β‚-
carbometoxy-3β‚-(4-iodophenyl) nortropane (FP-CIT) demonstrated
reduced striatal dopamine transporter binding in DLB compared with
AD
13–16
and a more marked symmetrical reduction of dopamine
transporter compared with early Parkinson’s disease (PD).
17,18
At present, the most studied technique for assessing dopaminergic
a. Normal FP-CIT uptake in a patient with Alzheimer’s disease.
pathways is FP-CIT SPECT. FP-CIT has the advantage of a shorter
b. Reduced FP-CIT uptake in a patient with dementia with Lewy bodies.
period of delay between the injection of the ligand and imaging
(three to six hours) compared with b-CIT SPECT (18–24 hours; see defined as reduced DAT binding in the posterior putamen on one
Figure 1). side, the sensitivity increased to 100% at the expense of some
loss of specificity, 92%.
O’ Brien et al.
19
reported both semi-quantitative and visual analysis of
FP-CIT SPECT of a large cohort of 164 subjects (23 DLB, 34 AD, 36 PD Important data come from a large European multicentre study
20
in
dementia [PDD], 38 PD and 33 healthy controls). When comparing which participants were scanned with FP-CIT SPECT after a
AD and DLB, the semi-quantitative analysis had a sensitivity of 78% consensus diagnosis was made by a panel of experts. Of the 288
and specificity of 85%, and visual rating had a sensitivity of 78% and patients included in the efficacy analysis, 88 were diagnosed with
specificity of 94%. However, DAT loss did not provide good diagnostic probable DLB, 56 with possible DLB and 144 with non-DLB. The scans
separation between DLB, PD and PDD. were visually rated by three independent nuclear medicine
specialists. When probable DLB patients were compared with
In a cohort with subsequent autopsy confirmation of diagnosis, non-DLB patients, the sensitivity of scanning was 77.7% and the
FP-CIT SPECT substantially enhanced the accuracy of diagnosis of specificity was 90.4%. Only 38% of possible DLB cases had an
DLB in comparison with clinical criteria alone.
4
The sensitivity of an abnormal FP-CIT SPECT image. One-year follow-up of the possible
DLB cases showed that FP-CIT SPECT at baseline had a sensitivity of
63% and a specificity of 100% for probable DLB diagnosis.
21
These
In a cohort with subsequent autopsy
studies are summarised in Table 2.
confirmation of diagnosis, FP-CIT single
In a review article, Booji and Kemp
22
discussed the observed 10%
photon emission computed tomography
increase of striatal FP-CIT binding ratios in patients using selective
substantially enhanced the accuracy of
serotonin re-uptake inhibitors (SSRIs) and serotonin and
norepinephrine re-uptake inhibitors (SNRIs).
23
They considered that
diagnosis of dementia with Lewy bodies
this increase is too small to be misinterpreted on a visually rated scan.
in comparison with clinical criteria alone.
However, there is a possibility that SSRIs and SNRIs could significantly
affect semi-quantitative analysis; this needs to be taken into account
in research settings when a semi-quantitative analysis may be
initial clinical diagnosis of DLB was 75% and the specificity was performed in addition to visual rating.
42%. The sensitivity for the diagnosis of DLB of an abnormal FP-CIT
scan, defined as total (bilateral) posterior putamen binding less than Efficacy of Post-synaptic Dopamine Imaging
two standard deviations below the mean of controls, was 88%, and The only study
24
specifically designed to investigate the post-synaptic
the specificity was 100%. Visual assessment of scans had a dopamine D2 neuroreceptor availability in the striatum in DLB used
sensitivity of 88% and specificity of 83%. When an abnormal scan was [
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I]-iodobenzamide (IBZM) SPECT and showed reduced radioactivity
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