Dopamine transporter binding in symptomatic controls and healthy volunteers: Considerations for neuroimaging trials

Honkanen, Emma A.; Eklund, Mikael; Nuuttila, Simo; Noponen, Tommi; Jaakkola, Elina; Mäkinen, Elina; Hirvilammi, Risto; Seppänen, Marko; Lindholm, Kari; Scheperjans, Filip; Parkkola, Riitta; Joutsa, Juho; Varrone, Andrea; Kaasinen, Valtteri

doi:10.1016/j.nicl.2021.102807

Cited by 3 publications

(4 citation statements)

References 25 publications

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“…Therefore, our study confirms that striatal monoamine availability in DIP is normal. However, our result differs from that of a recent study of dopamine transporters in symptomatic controls and healthy subjects that found symptomatic controls with essential tremor, vascular parkinsonism, or DIP to show higher putaminal dopamine transporter binding than healthy subjects 7 . Heterogeneity of symptomatic controls and selection bias in enrolling healthy subjects might explain that conflicting result.…”

Section: Discussioncontrasting

confidence: 99%

Decreased thalamic monoamine availability in drug-induced parkinsonism

Yoo

Lyoo

et al. 2022

Sci Rep

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Drug-induced parkinsonism (DIP) is caused by a dopamine receptor blockade and is a major cause of misleading diagnosis of Parkinson’s disease (PD). Striatal dopamine activity has been investigated widely in DIP; however, most studies with dopamine transporter imaging have focused on the clinical characteristics and prognosis. This study investigated differences in striatal subregional monoamine availability among patients with DIP, normal controls, and patients with early PD. Thirty-five DIP patients, the same number of age-matched PD patients, and 46 healthy controls were selected for this study. Parkinsonian motor status was examined. Brain magnetic resonance imaging and positron emission tomography with 18F-N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane were performed, and the regional standardized uptake values were analyzed with a volume-of-interest template and compared among the groups. The groups were evenly matched for age, but there were numerically more females in the DIP group. Parkinsonian motor symptoms were similar in the DIP and PD groups. Monoamine availability in the thalamus of the DIP group was lower than that of the normal controls and similar to that of the PD group. In other subregions (putamen, globus pallidus, and ventral striatum), monoamine availability in the DIP group and normal controls did not differ and was higher than that in the PD group. This difference compared to healthy subject suggests that low monoamine availability in the thalamus could be an imaging biomarker of DIP.

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Section: Discussioncontrasting

confidence: 99%

Decreased thalamic monoamine availability in drug-induced parkinsonism

Yoo

Lyoo

et al. 2022

Sci Rep

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“…The mean putamen and posterior-putamen SBR values were similar to those previously published [ 12 ]. These results are not consistent with those of a recent study [ 14 ] showing that the mean SBR values of Hv ( n = 48) and of patients without dopaminergic degeneration ( n = 70) were similar for all VOIs except for the posterior putamen VOI for which values were 8% higher for the patients. As suggested by the authors, this difference could be explained by a selection bias, thereby highlighting the importance of a large sample size.…”

Section: Discussioncontrasting

confidence: 99%

“…No significant difference was observed between databases from Hv and those from patients without dopaminergic neurodegenerative pathology. However, these results are still debated, as SBR could also depend on comorbidities; recent study found that the mean posterior putamen SBR value was 8% higher in a group of symptomatic patients without dopaminergic neurodegenerative pathology than in a group of Hv [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Semi-quantitative analysis of visually normal 123I-FP-CIT across three large databases revealed no difference between control and patients

et al. 2023

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Background To show the equivalence between the specific binding ratios (SBR) of visually normal 123I-FP-CIT SPECT scans from patients to those from healthy volunteers (Hv) or patients without dopaminergic degeneration to allow their use as a reference database. Methods The SBR values of visually normal SPECT scans from 3 groups were studied: (1) suspected Parkinsonism and no diagnostic follow-up (ScanOnlyDB: n = 764, NM/CT 670 CZT, GE Healthcare), (2) no degenerative dopaminergic pathology after a 5-year follow-up (NoDG5YearsDB: n = 237, Symbia T2, Siemens Medical Solutions), and 3) Hv (HvDB: n = 118, commercial GE database). A general linear model (GLM) was constructed with caudate, putamen, and striatum SBR as the dependent variables, and age and gender as the independent variables. Following post-reconstruction harmonization of the data, DB were combined in pairs, ScanOnlyDB&NoDG5yearsDG and ScanOnlyDB&HvDB before performing GLM analysis. Additionally, ScanOnlyDB GLM estimates were compared to those published from Siemens commercial DB (SiemensDB) and ENC-DAT. Results The dispersion parameters, R2 and the SBR coefficients of variation, did not differ between databases. For all volumes of interest and all databases, SBR decreased significantly with age (e.g., decrease per decade for the striatum: − 4.94% for ScanOnlyDB, − 4.65% for NoDG5YearsDB, − 5.69% for HvDB). There was a significant covariance between SBR and gender for ScanOnlyDB (P < 10–5) and NoDG5YearsDB (P < 10–2). The age-gender interaction was significant only for ScanOnlyDB (P < 10–2), and the p-value decreased to 10–6 after combining ScanOnlyDB with NoDG5YearsDB. ScanOnlyDB GLM estimates were not significantly different from those from SiemensDB or ENC-DAT except for age-gender interaction. Conclusion SBR values distribution from visually normal scans were not different from the existing reference database, enabling this method to create a reference database by expert nuclear physicians. In addition, it showed a rarely described age-gender interaction related to its size. The proposed post-reconstruction harmonization method can also facilitate the use of semi-quantitative analysis.

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“…With the development of molecular imaging, DAT uptake levels have become a reliable indicator for evaluating PD progression [ 15 ]. This is a more objective approach than the UPDRS score and is rarely used to assess the effects of antihypertensive drugs on PD [ 7 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Antihypertensive drugs may not delay the symptom progression of Parkinson’s disease: A 2-year follow-up study

Dong

Zuo

Zhong

et al. 2023

Heliyon

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Dopamine transporter binding in symptomatic controls and healthy volunteers: Considerations for neuroimaging trials

Abstract: Highlights Symptomatic controls have higher putaminal DAT binding than healthy controls. The difference could be due to selection/self-selection bias or upregulation. The effect should be taken into account when neuroimaging trials are designed.

Cited by 3 publications

References 25 publications

Decreased thalamic monoamine availability in drug-induced parkinsonism

Decreased thalamic monoamine availability in drug-induced parkinsonism

Semi-quantitative analysis of visually normal 123I-FP-CIT across three large databases revealed no difference between control and patients

Antihypertensive drugs may not delay the symptom progression of Parkinson’s disease: A 2-year follow-up study

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