scholarly journals Molecular Imaging of the Dopamine Transporter

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 872 ◽  
Author(s):  
Palermo ◽  
Ceravolo
Keyword(s):  
Dopamine Transporter ◽  
Single Photon ◽  
Photon Emission ◽  
Surrogate Marker ◽  
Neuronal Loss ◽  
Drug Induced ◽  
Regulatory Changes ◽  
Quantitative Measurements ◽  
Dat Spect

Dopamine transporter (DAT) single-photon emission tomography (SPECT) with (123)Ioflupane is a widely used diagnostic tool for patients with suspected parkinsonian syndromes, as it assists with differentiating between Parkinson’s disease (PD) or atypical parkinsonisms and conditions without a presynaptic dopaminergic deficit such as essential tremor, vascular and drug-induced parkinsonisms. Recent evidence supports its utility as in vivo proof of degenerative parkinsonisms, and DAT imaging has been proposed as a potential surrogate marker for dopaminergic nigrostriatal neurons. However, the interpretation of DAT-SPECT imaging may be challenged by several factors including the loss of DAT receptor density with age and the effect of certain drugs on dopamine uptake. Furthermore, a clear, direct relationship between nigral loss and DAT decrease has been controversial so far. Striatal DAT uptake could reflect nigral neuronal loss once the loss exceeds 50%. Indeed, reduction of DAT binding seems to be already present in the prodromal stage of PD, suggesting both an early synaptic dysfunction and the activation of compensatory changes to delay the onset of symptoms. Despite a weak correlation with PD severity and progression, quantitative measurements of DAT binding at baseline could be used to predict the emergence of late-disease motor fluctuations and dyskinesias. This review addresses the possibilities and limitations of DAT-SPECT in PD and, focusing specifically on regulatory changes of DAT in surviving DA neurons, we investigate its role in diagnosis and its prognostic value for motor complications as disease progresses.

scholarly journals Dopamine transporter imaging in neurodegenerative movement disorders: PET vs. SPECT

2020 ◽  
Vol 8 (5) ◽  
pp. 349-356
Author(s):  
Vera S. Kerstens ◽  
A. Varrone
Keyword(s):  
Dopamine Transporter ◽  
Pet Imaging ◽  
Single Photon ◽  
Relevant Literature ◽  
Photon Emission ◽  
Active Role ◽  
Emission Computed Tomography ◽  
Parkinsonian Syndromes ◽  
Dat Spect

Abstract Purpose The dopamine transporter (DAT) serves as biomarker for parkinsonian syndromes. DAT can be measured in vivo with single-photon emission computed tomography (SPECT) and positron emission tomography (PET). DAT-SPECT is the current clinical molecular imaging standard. However, PET has advantages over SPECT measurements, and PET radioligands with the necessary properties for clinical applications are on the rise. Therefore, it is time to review the role of DAT imaging with SPECT compared to PET. Methods PubMed and Web of Science were searched for relevant literature of the previous 10 years. Four topics for comparison were used: diagnostic accuracy, quantitative accuracy, logistics, and flexibility. Results There are a few studies directly comparing DAT-PET and DAT-SPECT. PET and SPECT both perform well in discriminating neurodegenerative from non-neurodegenerative parkinsonism. Clinical DAT-PET imaging seems feasible only recently, thanks to simplified DAT assessments and better availability of PET radioligands and systems. The higher resolution of PET makes more comprehensive assessments of disease progression in the basal ganglia possible. Additionally, it has the possibility of multimodal target assessment. Conclusion DAT-SPECT is established for differentiating degenerative from non-degenerative parkinsonism. For further differentiation within neurodegenerative Parkinsonian syndromes, DAT-PET has essential benefits. Nowadays, because of wider availability of PET systems and radioligand production centers, and the possibility to use simplified quantification methods, DAT-PET imaging is feasible for clinical use. Therefore, DAT-PET needs to be considered for a more active role in the clinic to take a step forward to a more comprehensive understanding and assessment of Parkinson’s disease.

scholarly journals Dopamine transporter imaging in clinically unclear cases of parkinsonism and the importance of Scans Without Evidence of Dopaminergic Deficit (SWEDDs)

2012 ◽  
Vol 70 (9) ◽  
pp. 667-673 ◽  
Author(s):  
Marco A. T. Utiumi ◽  
André C. Felício ◽  
Conrado R. Borges ◽  
Vera L. Braatz ◽  
Sheyla A. S. Rezende ◽  
...  
Keyword(s):  
Dopamine Transporter ◽  
Single Photon ◽  
Imaging Techniques ◽  
Photon Emission ◽  
Cost Effective ◽  
Emission Computed Tomography ◽  
Parkinsonian Syndromes ◽  
Cost Effective Technique ◽  
Dat Spect

The clinical diagnosis of Parkinson's disease (PD) is susceptible to misdiagnosis, especially in the earlier stages of the disease. Recently, in vivo imaging techniques assessing the presynaptic dopamine transporter (DAT) have emerged as a useful tool in PD diagnosis, improving its accuracy. OBJECTIVE: It was to illustrate the clinical usefulness of a brain single-photon emission computed tomography (SPECT) DAT ligand, and highlight relevant aspects of scans without evidence of dopaminergic deficit (SWEDDs) in this context. CASES: We described four representative patients with clinically unclear parkinsonian syndromes who underwent [99mTc]-TRODAT-1 SPECT and reviewed the clinical implications. CONCLUSION: DAT-SPECT is an important, cost-effective, technique for the differential diagnosis of parkinsonian syndromes. Additionally, SWEDD cases present clinical and paraclinical peculiarities that may retrospectively identify them as essential/dystonic tremor. The lack of histopathological data limits further conclusions.

scholarly journals Imaging Amyloid-β Deposits In Vivo

2002 ◽  
Vol 22 (9) ◽  
pp. 1035-1041 ◽  
Author(s):  
Brian J. Bacskai ◽  
William E. Klunk ◽  
Chester A. Mathis ◽  
Bradley T. Hyman
Keyword(s):  
Single Photon ◽  
Senile Plaques ◽  
Photon Emission ◽  
Multiphoton Microscopy ◽  
Amyloid Β ◽  
Neuronal Loss ◽  
High Sensitivity ◽  
Emission Computed Tomography ◽  
Tissue Samples

Alzheimer disease (AD) is an illness that can only be diagnosed with certainty with postmortem examination of brain tissue. Tissue samples from afflicted patients show neuronal loss, neurofibrillary tangles (NFTs), and amyloid-β plaques. An imaging technique that permitted in vivo detection of NFTs or amyloid-β plaques would be extremely valuable. For example, chronic imaging of senile plaques would provide a readout of the efficacy of experimental therapeutics aimed at removing these neuropathologic lesions. This review discusses the available techniques for imaging amyloid-β deposits in the intact brain, including magnetic resonance imaging, positron emission tomography, single photon emission computed tomography, and multiphoton microscopy. A variety of agents that target amyloid-β deposits specifically have been developed using one or several of these imaging modalities. The difficulty in developing these tools lies in the need for the agents to cross the blood-brain barrier while recognizing amyloid-β with high sensitivity and specificity. This review describes the progress in developing reagents suitable for in vivo imaging of senile plaques.

Reduced in vivo binding to the serotonin transporter in the cerebral cortex of MDMA (‘ecstasy’) users

1999 ◽  
Vol 175 (1) ◽  
pp. 63-69 ◽  
Author(s):  
David M. Semple ◽  
Klaus P. Ebmeier ◽  
Michael F. Glabus ◽  
Ronan E. O'Carroll ◽  
Eve C. Johnstone
Keyword(s):  
Dopamine Transporter ◽  
Serotonin Transporter ◽  
Single Photon ◽  
Psychiatric Morbidity ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
Cross Sectional ◽  
Lenticular Nuclei

BackgroundThe use of MDMA (‘ecstasy’) is common among young people in Western countries. Animal models of MDMA toxicity suggest a loss of serotonergic neurons, and potentially implicate it in the development of significant psychiatric morbidity in humans.AimsTo test whether long-term use of MDMA can produce abnormalities in cerebral serotonin, but not dopamine, transporter binding measured by single photon emission computed tomography (SPECT)MethodTen male regular ecstasy users and 10 well-matched controls recruited from the same community sources participated in SPECT with the serotonin transporter (SEPT) ligand [123I]-CIT. Dopamine transporter binding was determined from scans acquired 23 hours after injection of the tracer.ResultsEcstasy users showed a cortical reduction of SERT binding, particularly prominent in primary sensory-motor cortex, with normal dopamine transporter binding in lenticular nuclei.ConclusionsThis cross-sectional association study provides suggestive evidence for specific, at least temporary, serotonergic neurotoxicity of MDMA in humans.

scholarly journals Substantia nigra micro-haemorrhage causing ipsilateral unilateral Parkinsonism and abnormal dopamine transporter scan uptake

2020 ◽  
pp. 20200118
Author(s):  
Aliaa Ghoneim ◽  
Christopher Pollard ◽  
Alok Tyagi ◽  
Ravi Jampana
Keyword(s):  
Substantia Nigra ◽  
Movement Disorder ◽  
Dopamine Transporter ◽  
Single Photon ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
Small Lesion ◽  
Nigrostriatal Pathway ◽  
Drug Induced ◽  
Complementary Role

Parkinsonism is a commonly seen movement disorder syndrome with neurodegenerative and non-neurodegenerative causes. Presynaptic dopamine transporter (DaT) single‐photon emission computed tomography (SPECT) imaging is the most commonly used imaging technique in clinical practice to differentiate degenerative Parkinson’s disease (PD) and PD plus syndromes from other causes such as essential tremor and drug-induced parkinsonism. This can help identify the patients who would benefit from medical therapy due to underlying pre-synaptic dopaminergic deficits. We report a case of unilateral parkinsonism caused by ipsilateral substantia nigra micro-haemorrhage resulting in disruption of the nigrostriatal pathway. This is an unusual case of a 55-year-old male patient who presented with unilateral Parkinsonism a decade after significant head trauma where MRI plays a critical and complementary role in diagnosing complete interruption of the nigrostriatal pathway due to cerebral micro-haemorrhage. The case also beautifully demonstrates the anatomy of the nigrostriatal pathway where a small lesion in the substantia nigra caused complete loss of radioligand uptake in the ipsilateral corpus striatum. Physicians should be aware of the importance of structural imaging in atypical movement disorder cases and, in particular, the routine use of susceptibility-weighted sequences (SWI).

scholarly journals Evaluating dopamine transporter imaging as an enrichment biomarker in a phase 2 Parkinson’s disease trial

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
R. Matthew Hutchison ◽  
Karleyton C. Evans ◽  
Tara Fox ◽  
Minhua Yang ◽  
Jerome Barakos ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Clinical Trial ◽  
Parkinson's Disease ◽  
Dopamine Transporter ◽  
Single Photon ◽  
Photon Emission ◽  
Alpha Synuclein ◽  
Emission Computed Tomography ◽  
Phase 2 ◽  
Dat Spect

Abstract Background Dopamine transporter single-photon emission computed tomography (DaT-SPECT) can quantify the functional integrity of the dopaminergic nerve terminals and has been suggested as an imaging modality to verify the clinical diagnosis of Parkinson’s disease (PD). Depending on the stage of progression, approximately 5–15% of participants clinically diagnosed with idiopathic PD have been observed in previous studies to have normal DaT-SPECT patterns. However, the utility of DaT-SPECT in enhancing early PD participant selection in a global, multicenter clinical trial of a potentially disease-modifying therapy is not well understood. Methods The SPARK clinical trial was a phase 2 trial of cinpanemab, a monoclonal antibody against alpha-synuclein, in participants with early PD. DaT-SPECT was performed at screening to select participants with DaT-SPECT patterns consistent with degenerative parkinsonism. Acquisition was harmonised across 82 sites. Images were reconstructed and qualitatively read at a central laboratory by blinded neuroradiologists for inclusion prior to automated quantitative analysis. Results In total, 482 unique participants were screened between January 2018 and May 2019; 3.8% (15/398) of imaged participants were excluded owing to negative DaT-SPECT findings (i.e., scans without evidence of dopaminergic deficit [SWEDD]). Conclusion A smaller proportion of SPARK participants were excluded owing to SWEDD status upon DaT-SPECT screening than has been reported in prior studies. Further research is needed to understand the reasons for the low SWEDD rate in this study and whether these results are generalisable to future studies. If supported, the radiation risks, imaging costs, and operational burden of DaT-SPECT for enrichment may be mitigated by clinical assessment and other study design aspects. Trial registration ClinicalTrials.gov identifier: NCT03318523. Date submitted: October 19, 2017. First Posted: October 24, 2017.

scholarly journals Practical Application of DaTQUANT with Optimal Threshold for Diagnostic Accuracy of Dopamine Transporter SPECT

Tomography ◽  
2021 ◽  
Vol 7 (4) ◽  
pp. 980-989
Author(s):  
Matthew Neill ◽  
Julia M. Fisher ◽  
Christine Brand ◽  
Hong Lei ◽  
Scott J. Sherman ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Dopamine Transporter ◽  
Sensitivity And Specificity ◽  
Single Photon ◽  
Photon Emission ◽  
Study Groups ◽  
Emission Computed Tomography ◽  
Single Variable ◽  
Dat Spect ◽  
Photon Emission Computed Tomography

Evaluation of Parkinsonian Syndromes (PS) with Ioflupane iodine-123 dopamine transporter single photon emission computed tomography (DaT-SPECT), in conjunction with history and clinical examination, aids in diagnosis. FDA-approved, semi-quantitative software, DaTQUANTTM (GE Healthcare, Chicago, IL, USA) is available to assist in interpretation. This study aims to evaluate the optimal variables and thresholds of DaTQUANT to yield the optimal diagnostic accuracy. It is a retrospective review with three different patient populations. DaT-SPECT images from all three study groups were evaluated using DaTQUANTTM software, and both single and multi-variable logistic regression were used to model PS status. The optimal models were chosen via accuracy, sensitivity, and specificity, then evaluated on the other study groups. Among single variable models, the posterior putamen yielded the highest accuracy (84% to 95%), while balancing sensitivity and specificity. Multi-variable models did not substantially improve the accuracy. When the optimal single variable models for each group were used to evaluate the remaining two groups, comparable results were achieved. In typical utilization of DaT-SPECT for differentiation between nigrostriatal degenerative disease (NSDD) and non-NSDD, the posterior putamen was the single variable that yielded the highest accuracy across three different patient populations. The posterior putamen’s recommended thresholds for DaTQUANT are SBR ≤ 1.0, z-score of ≤−1.8 and percent deviation ≤ −0.34.

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