Abstract:The longitudinal decline of striatal [F]FP-CIT uptake in PD was nonlinear and significantly faster than that in non-PD, with a different rate of decline among the striatal subregions.
“…4 . Yearly DAT decline in PD patients has been estimated to be between 5 and 13% in striatal regions [ 31 , 36 , 37 ], meaning that [ 18 F]FE-PE2I PET is well suited for measuring biological DAT differences in striatal regions in a longitudinal follow-up study with a typical sample size for PET studies. Fig.…”
Background: Reliable quantification of dopamine transporter (DAT), a biomarker for Parkinson's disease (PD), is essential for diagnostic purposes as well as for evaluation of potential disease-modifying treatment. Due to degeneration of dopaminergic neurons and thus lower expected radioligand binding to DAT, higher measurement variability in PD patients might be expected than earlier reproducibility results in healthy controls. Therefore, we aimed to examine the test-retest properties of [ 18 F]FE-PE2I-PET in PD patients. Methods: Nine patients with PD (Hoehn and Yahr stage < 3) were included (men/women 6/3; mean age 65.2 ± 6.8 years). Each patient underwent two [ 18 F]FE-PE2I-PET measurements within 7-28 days. The outcome measure was non-displaceable binding potential generated using wavelet-aided parametric imaging with cerebellum as reference region. We assessed test-retest performance using estimates of reliability and repeatability. Regions for primary analysis were caudate, putamen, ventral striatum, and substantia nigra. Exploratory analysis was performed for functional subdivisions of the striatum. We also compared the more vs. less affected side. Results: [ 18 F]FE-PE2I showed absolute variability estimates of 5.3-7.6% in striatal regions and 11% in substantia nigra and ICCs of 0.74-0.97 (median 0.91). The absolute variability for functional striatal subdivisions was 6.0-9.6% and ICCs of 0.76-0.91 (median 0.91). The less affected substantia nigra exhibited greater consistency than the more affected side. According to power calculations based on the current sample size, DAT changes of 5-11% in the striatum and 28% in the substantia nigra can be detected with a power of 0.8 (p < 0.0125). Conclusion: DAT-PET measurements with [ 18 F]FE-PE2I in PD patients showed good repeatability and reliability. The slightly lower reliability in the substantia nigra in patients may be explained by lower DAT density and smaller anatomical size. Power calculations suggest that [ 18 F]FE-PE2I PET is a suitable marker for longitudinal DAT decline in PD.
“…4 . Yearly DAT decline in PD patients has been estimated to be between 5 and 13% in striatal regions [ 31 , 36 , 37 ], meaning that [ 18 F]FE-PE2I PET is well suited for measuring biological DAT differences in striatal regions in a longitudinal follow-up study with a typical sample size for PET studies. Fig.…”
Background: Reliable quantification of dopamine transporter (DAT), a biomarker for Parkinson's disease (PD), is essential for diagnostic purposes as well as for evaluation of potential disease-modifying treatment. Due to degeneration of dopaminergic neurons and thus lower expected radioligand binding to DAT, higher measurement variability in PD patients might be expected than earlier reproducibility results in healthy controls. Therefore, we aimed to examine the test-retest properties of [ 18 F]FE-PE2I-PET in PD patients. Methods: Nine patients with PD (Hoehn and Yahr stage < 3) were included (men/women 6/3; mean age 65.2 ± 6.8 years). Each patient underwent two [ 18 F]FE-PE2I-PET measurements within 7-28 days. The outcome measure was non-displaceable binding potential generated using wavelet-aided parametric imaging with cerebellum as reference region. We assessed test-retest performance using estimates of reliability and repeatability. Regions for primary analysis were caudate, putamen, ventral striatum, and substantia nigra. Exploratory analysis was performed for functional subdivisions of the striatum. We also compared the more vs. less affected side. Results: [ 18 F]FE-PE2I showed absolute variability estimates of 5.3-7.6% in striatal regions and 11% in substantia nigra and ICCs of 0.74-0.97 (median 0.91). The absolute variability for functional striatal subdivisions was 6.0-9.6% and ICCs of 0.76-0.91 (median 0.91). The less affected substantia nigra exhibited greater consistency than the more affected side. According to power calculations based on the current sample size, DAT changes of 5-11% in the striatum and 28% in the substantia nigra can be detected with a power of 0.8 (p < 0.0125). Conclusion: DAT-PET measurements with [ 18 F]FE-PE2I in PD patients showed good repeatability and reliability. The slightly lower reliability in the substantia nigra in patients may be explained by lower DAT density and smaller anatomical size. Power calculations suggest that [ 18 F]FE-PE2I PET is a suitable marker for longitudinal DAT decline in PD.
“…We included the remaining 33 articles (six articles reported PET studies involving 779 patients with PD and 124 controls, and 27 reported SPECT studies involving 1244 PD patients and 859 controls) in this meta‐analysis. These studies comprised cross‐sectional surveys (10 studies), case‐control studies (19 studies), and cohort studies (four studies) 17,22–26,35–61 . Figure 1 illustrates the protocol for the literature search and study selection process.…”
Section: Resultsmentioning
confidence: 99%
“…As shown in Table 1, the number of participants in the other five included studies met the sample size requirements for a typical molecular imaging study 67–75 . With respect to individual studies, all included studies, except one (findings in the caudate nucleus in Sung’s study 24 ), reported a significant decrease in the SUVR for 18 F‐FP‐CIT uptake in the three striatum regions (caudate nucleus, anterior putamen, and posterior putamen) in patients with PD compared to that in the controls. Moreover, the overall effect size indicated significantly decreased 18 F‐FP‐CIT uptake in the targeted cerebral regions.…”
Section: Discussionmentioning
confidence: 99%
“…Previous studies have reported a significantly faster decrease in striatal 18 F‐FP‐CIT uptake in patients with PD compared to that in controls. Moreover, there are differences in the rates of decrease among the striatal subregions, namely, the caudate nucleus, anterior putamen, and posterior putamen, which indicate that 18 F‐FP‐CIT may be more effective for the diagnosis of PD 22–26 …”
Objective
18F‐FP‐CIT and 123I‐FP‐CIT are widely used radiotracers in molecular imaging for Parkinson’s disease (PD) diagnosis. Compared with 123I‐FP‐CIT, 18F‐FP‐CIT has superior tracer kinetics. We aimed to conduct a meta‐analysis to assess the efficacy of using 18F‐FP‐CIT positron emission tomography (PET) and 123I‐FP‐CIT single‐photon emission computed tomography (SPECT) of dopamine transporters in patients with PD in order to provide evidence for clinical decision‐making.
Methods
We searched the PubMed, Embase, Wanfang Data, and China National Knowledge Infrastructure databases to identify the relevant studies from the time of inception of the databases to 30 April 2020. We identified six PET studies, including 779 patients with PD and 124 healthy controls, which met the inclusion criteria. Twenty‐seven SPECT studies with 1244 PD patients and 859 controls were also included in this meta‐analysis.
Results
Overall effect‐size analysis indicated that patients with PD showed significantly reduced 18F‐FP‐CIT uptake in three brain regions [caudate nucleus: standardized mean difference (SMD) = −1.71, Z = −3.31, P = 0.0009; anterior putamen: SMD = −3.71, Z = −6.26, P < 0.0001; and posterior putamen: SMD = −5.49, Z = −5.97, P < 0.0001]. Significant decreases of 123I‐FP‐CIT uptake were also observed in the caudate (SMD = −2.31, Z = −11.49, P < 0.0001) and putamen (SMD = −3.25, Z = −14.79, P < 0.0001).
Interpretation
In conclusion, our findings indicate that both 18F‐FP‐CIT PET and 123I‐FP‐CIT SPECT imaging of dopamine transporters can provide viable biomarkers for early PD diagnosis.
“…The relationship between sample size and effect size was examined as a function of statistical power and is presented in Figure 4. Yearly DAT-decline in PD-patients has been estimated to be between 5 and 13% in striatal regions [31,36,37], meaning that [ 18 F]FE-PE2I PET is well suited for measuring biological DAT-differences in striatal regions in a longitudinal follow-up study with a typical sample size for PET studies. Representative test and retest parametric BPND images of [18F]FE-PE2I.…”
Background. Reliable quantification of dopamine transporter (DAT), a biomarker for Parkinson’s disease (PD), is essential for diagnostic purposes as well as for evaluation of potential disease-modifying treatment. Due to degeneration of dopaminergic neurons and thus lower expected radioligand binding to DAT, higher measurement variability in PD patients might be expected than earlier reproducibility results in healthy controls. Therefore, we aimed to examine the test-retest properties of [18F]FE-PE2I-PET in PD patients. Methods. Nine patients with PD (Hoehn & Yahr stage < 3) were included (men/women: 6/3; mean age 65.2±6.8y). Each patient underwent two [18F]FE-PE2I-PET measurements within 7–28 days. The outcome measure was non-displaceable binding potential generated using wavelet-aided parametric imaging with cerebellum as reference region. We assessed test-retest performance using estimates of reliability and repeatability. Regions for primary analysis were caudate, putamen, ventral striatum, and substantia nigra. Exploratory analysis was performed for functional subdivisions of the striatum. We also compared the more vs. less-affected side.Results. [18F]FE-PE2I showed absolute variability estimates of 5.3–7.6% in striatal regions and 11% in substantia nigra, and ICCs of 0.74—0.97 (median: 0.91). The absolute variability for functional striatal subdivisions was 6.0–9.6% and ICCs of 0.76–0.91 (median: 0.91). The less affected substantia nigra exhibited greater consistency than the more affected side. According to power calculations based on the current sample size, DAT changes of 5–11% in the striatum and 28% in the substantia nigra can be detected with a power of 0.8 (p<0.0125). Conclusion. DAT-PET measurements with [18F]FE-PE2I in PD patients showed good repeatability and reliability. The slightly lower reliability in the substantia nigra in patients may be explained by lower DAT density and smaller anatomical size. Power calculations suggest that [18F]FE-PE2I PET is a suitable marker for longitudinal DAT decline in PD.Trial registration number: EudraCT 2017-003327-29
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