Table 1.
DAT imaging as a predictive biomarker in PD: motor and non-motor outcomes.
| Outcomes | Authors and Year | Type of Study | Radioligand | Population | Main Results |
|---|---|---|---|---|---|
| Motor Severity | |||||
| UPDRS motor score, Hoen and Yahr scale, Freezing of gait, Falling | Vogt et al., 2011 [224] | Prospective | [123I]-β-CIT SPECT | 44 early-stage PD | Weak correlation between baseline DAT binding ratios and staging parameters (UPDRS II-III and H&Y) at follow-up |
| Ravina et al., 2012 [43] | Prospective | [123I]-β-CIT SPECT | 491 de novo PD | Lower baseline DAT binding is associated with higher risk for motor-related disability, falling and postural instability | |
| Rahmim et al., 2016 [227] | Prospective | [123I]-FP-CIT SPECT | 64 de novo PD | Baseline DAT binding is significantly correlated with UPDRS III and disease duration | |
| Djaldetti et al., 2018 [222] | Retrospective | [123I]-FP-CIT SPECT | 41 early-stage PD | Baseline DAT binding does not predict H&Y or UPDRS motor score progression, but lower DAT uptake at baseline is associated with the development of FOG | |
| Kim et al., 2018 [219] | Retrospective | [123I]-FP-CIT SPECT | 390 de novo PD | Lower baseline DAT binding in the caudate nucleus and putamen significantly predicts the development of FOG | |
| Simuni et al., 2018 [70] | Prospective | [123I]-FP-CIT SPECT | 358 early-stage PD | No correlation between the rate of change of UPDRS-III and change in the striatal DAT uptake | |
| Li et al., 2018 [184] | Prospective | 11C-PE2I PET | 33 mild-moderate stage PD | Negative correlation between baseline DAT binding in the caudate, anterior and posterior putamen, and motor severity (UPDRS-III, bradykinesia-rigidity subscores) | |
| Kim et al., 2019 [219] | Prospective | [123I]-FP-CIT SPECT | 392 early-stage PD | Baseline caudate DAT binding significantly predicts FOG | |
| Pagano et al., 2019 [230] | Prospective | 11C-PE2I PET | 17 de novo PD, 15 early-stage LD-treated PD, 24 moderate-advanced LD-treated PD |
Negative correlation between change in motor severity (UPDRS-III and bradykinesia/rigidity subscores) and change in the baseline DAT uptake in the caudate and posterior putamen | |
| Survival | Makinen et al., 2017 [228] | Retrospective | [123I]-FP-CIT SPECT | 162 PD: all stages | Baseline DAT binding does not predict mortality |
| Motor complications | |||||
| Levodopa-induced dyskinesia (LID) Motor fluctuations |
Hong et al., 2014 [87] | Prospective | 18F-FP-CIT PET | 127 de novo PD | Baseline putaminal DAT uptake significantly predicts the development of LID |
| Palermo et al. 2020 [88] | Retrospective | [123I]-FP-CIT SPECT | 105 de novo PD | Lower baseline DAT binding in early-onset PD predicts later motor complications | |
| Yoo et al., 2017 [233] | Retrospective | 18F-FP-CIT PET | 65 de novo PD | Lower DAT binding in the posterior putamen at baseline is a major risk factor for earlier onset of LID | |
| Jeong et al., 2018 [234] | Prospective | [123I]-FP-CIT SPECT | 290 de novo PD | Baseline DAT binding is lower in PD patients who will develop LID | |
| Chung et al., 2018 [235] | Retrospective | 18F-FP-CIT PET | 342 de novo PD | Lower baseline DAT binding in the anterior putamen predicts the wearing-off phenomenon | |
| Djaldetti et al., 2018 [222] | Retrospective | [123I]-FP-CIT SPECT | 41 early-stage PD | Baseline DAT binding does not predict motor complications | |
| Roussakis et al., 2019 [236] | Prospective | [123I]-FP-CIT SPECT | 42 de novo PD | Baseline DAT binding does not predict LID | |
| Chung et al., 2020 [237] | Retrospective | 18F-FP-CIT PET | 205 early-stage PD | Baseline DAT binding, particularly in the anterior putamen, predicts the wearing-off phenomenon | |
| Non-motor symptoms | |||||
| Anxiety, Depression, Impulsivity, Constipation, Autonomic symptoms, Visual hallucinations, Body weight gain/loss | Ravina et al., 2012 [43] | Prospective | [123I]-β-CIT SPECT | 491 de novo PD | Lower striatal DAT binding at baseline is associated with depressive symptoms |
| Kyoungjune et al., 2019 [238] | Prospective | [123I]-FP-CIT SPECT | 163 de novo PD | Lower baseline putamen-to-caudate DAT binding ratio is associated with future weight gain in men (but not women) | |
| La Torre et al., 2020 [239] | Prospective | [123I]-FP-CIT SPECT | 20 de novo PD | Higher baseline putamen-to-caudate DAT binding ratios are associated with higher emotional responsiveness and higher non-planning impulsivity | |
| Hinkle et al., 2018 [240] | Prospective | [123I]-FP-CIT SPECT | 397 de novo PD | Constipation is closely associated with lower baseline caudate DAT binding | |
| Jaakkola et al., 2017 [241] | Prospective | [123I]-FP-CIT SPECT | 70 early-stage PD | Baseline low ventral striatal DAT binding is associated with visual hallucinations | |
| Cognitive performances | |||||
| Ravina et al., 2012 [43] | Prospective | [123I]-β-CIT SPECT | 491 de novo PD | Lower striatal DAT binding at baseline is associated with cognitive impairment | |
| Arnaldi et al., 2017 [242] | Prospective | [123I]-FP-CIT SPECT | 54 de novo PD | Caudate DAT binding predicts patients’ cognitive worsening at the follow up | |
| Yousaf et al., 2019 [68] | Prospective | [123I]-FP-CIT SPECT | 262 de novo PD | Lower caudate DAT binding at baseline is associated with higher risk of cognitive impairment |
Retrospective and prospective longitudinal studies evaluating the putative predictive role of baseline striatal DAT binding in PD. Abbreviations: DAT, dopamine active transporter; UPDRS, Unified Parkinson’s Disease Rating Scale; PD, Parkinson’s disease; H&Y, Hoen and Yahr; FOG, freezing of gait; LD, Levodopa; LID, Levodopa-induced dyskinesia; MCI, Mild cognitive impairment.