Residency · Residency · Nuclear Medicine

DaTscan: Dopamine Transporter Imaging

Introduction

DaTscan (I-123 ioflupane) is a SPECT radiopharmaceutical that binds to presynaptic dopamine transporters (DAT) in the striatum. It is the only FDA-approved imaging agent for evaluating the integrity of the nigrostriatal dopaminergic pathway. DaTscan plays a critical role in distinguishing neurodegenerative parkinsonian syndromes from conditions that lack a dopaminergic deficit, such as essential tremor or drug-induced parkinsonism.

Physiological Basis

The Nigrostriatal Pathway

Dopaminergic neurons originate in the substantia nigra pars compacta and project to the striatum, which comprises the caudate nucleus and putamen. Dopamine transporters are located on presynaptic nerve terminals and regulate dopamine reuptake. In Parkinson disease and related disorders, progressive loss of dopaminergic neurons leads to reduced DAT density. By the time motor symptoms appear, DAT loss is typically greater than 50%. The putamen is affected earlier and more severely than the caudate.

I-123 Ioflupane Mechanism

Ioflupane is a cocaine analog with high affinity for DAT. Labeled with I-123 (half-life 13.2 hours, 159 keV gamma emission), it binds to DAT on presynaptic striatal nerve terminals. The degree of uptake reflects the density of intact dopaminergic nerve terminals.

Clinical Indications

DaTscan is indicated for differentiating essential tremor from parkinsonian syndromes, evaluating patients with a clinically uncertain parkinsonian syndrome, and distinguishing dementia with Lewy bodies from Alzheimer disease. It is not indicated for differentiating between the various parkinsonian syndromes (Parkinson disease versus multiple system atrophy versus progressive supranuclear palsy versus corticobasal degeneration), as all of these conditions show reduced DAT.

Patient Preparation and Protocol

Pre-Imaging Preparation

Thyroid blockade must be administered before injection to prevent thyroid uptake of free I-123. Options include potassium iodide (SSKI), Lugol solution, or potassium perchlorate. Blockade should begin at least 1 hour before injection and continue for 24 to 48 hours afterward. The medication list must be reviewed for drugs that interfere with DAT binding.

Medications That Affect DaTscan

Medications that must be discontinued include cocaine, methylphenidate, amphetamines, bupropion, benzatropine, modafinil, and phentermine. Medications that do not need to be discontinued include levodopa, dopamine agonists, MAO-B inhibitors, COMT inhibitors, and SSRIs (which have minimal effect). The discontinuation period is generally 5 half-lives.

Imaging Protocol

The dose is 3 to 5 mCi (111 to 185 MBq) of I-123 ioflupane administered intravenously. The uptake period is 3 to 6 hours post-injection. SPECT acquisition uses low-energy high-resolution (LEHR) collimators with 120 to 128 projections at 30 to 45 seconds per stop. Reconstruction employs filtered back projection or iterative methods with attenuation correction.

Image Interpretation

Normal Scan

A normal scan shows comma-shaped or crescent-shaped bilateral striatal uptake. Both the caudate (head) and putamen (tail) are well visualized. Activity is symmetric between left and right striata. The appearance is often described as a "comma" or "bird" pattern.

Abnormal Patterns

The earliest abnormality in Parkinson disease is putaminal loss, producing an egg or period shape with reduced uptake in the posterior putamen and preserved caudate uptake. Asymmetric loss is typical, usually contralateral to the more symptomatic side. A dot or period pattern represents severe loss leaving only caudate uptake. Near-complete loss with minimal residual striatal uptake occurs in advanced disease.

Semi-Quantitative Analysis

The striatal binding ratio (SBR) is calculated as (striatum minus background) divided by background, using the occipital cortex as the reference region since it is devoid of DAT. Age-adjusted normative values should be applied. SBR values below 65% of age-expected normal are considered abnormal. The caudate-to-putamen ratio may help identify early putaminal loss.

Clinical Scenarios

Essential Tremor vs. Parkinson Disease

Essential tremor produces a normal DaTscan because there is no dopaminergic deficit. Parkinson disease produces an abnormal DaTscan with asymmetric putaminal loss. DaTscan has a sensitivity greater than 95% and specificity greater than 90% for this distinction.

Dementia with Lewy Bodies vs. Alzheimer Disease

Dementia with Lewy bodies produces an abnormal DaTscan because a dopaminergic deficit is present. Alzheimer disease produces a normal DaTscan. DaTscan is included in the revised diagnostic criteria for DLB as an indicative biomarker.

Drug-Induced Parkinsonism

Drug-induced parkinsonism typically produces a normal DaTscan because the mechanism involves postsynaptic dopamine receptor blockade rather than presynaptic neuronal loss. This helps differentiate it from true neurodegenerative parkinsonism. However, some patients with drug-induced symptoms may have underlying Parkinson disease unmasked by the medication.

Limitations

DaTscan cannot differentiate between Parkinson disease, multiple system atrophy, progressive supranuclear palsy, or corticobasal degeneration, as all show reduced DAT. The scan reflects DAT density, not dopamine levels. False negatives are possible in very early disease (scans without evidence of dopaminergic deficit, or SWEDD). False positives can occur with medications that block DAT.

Clinical Pearls

DaTscan differentiates conditions with dopaminergic deficit (Parkinson disease, DLB, MSA, PSP) from those without (essential tremor, drug-induced parkinsonism), but it cannot distinguish among the neurodegenerative parkinsonian disorders themselves.

Thyroid blockade is mandatory to prevent thyroid irradiation from free I-123. Failure to administer it is a protocol error.

The putamen is affected before the caudate in Parkinson disease. Subtle asymmetric putaminal loss on DaTscan represents the earliest detectable abnormality.

References

1. Defined Appropriate Use Criteria for DaTscan Imaging. Neurology. 2021;96(7):e1025-e1032.
2. Defined Clinical Utility of I-123 Ioflupane SPECT in Movement Disorders. Journal of Nuclear Medicine. 2020;61(4):552-559.
3. Defined Role of DaTscan in the Diagnosis of Dementia with Lewy Bodies. European Journal of Nuclear Medicine and Molecular Imaging. 2019;46:1547-1560.
4. Defined Semi-Quantitative Analysis Methodology for DaTscan. Clinical Nuclear Medicine. 2021;46(3):e131-e138.

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