Brain ¹⁸F-DOPA PET/CT in the diagnosis of Parkinson’s disease

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Introduction

Parkinson’s disease (PD) is a progressive neurodegenerative disorder, ranking as the second most prevalent condition worldwide after Alzheimer’s disease. The pathomorphological basis of PD involves the degeneration of dopaminergic neurons in the pars compacta of the substantia nigra and the formation of cytoplasmic inclusions — Lewy bodies — within neurons, primarily composed of aggregated alpha-synuclein protein. Clinical manifestation occurs when 50–70% of nigrostriatal neurons are lost and is characterized by the classic motor triad of PD symptoms: bradykinesia, resting tremor, and muscle rigidity [1–3].

Despite the well-defined clinical presentation of PD at advanced stages, diagnosis in early stages faces significant challenges due to a prolonged preclinical period and the nonspecific nature of early non-motor symptoms. A particular diagnostic difficulty lies in differentiating PD from atypical parkinsonism syndromes (multiple system atrophy, progressive supranuclear palsy), essential tremor, and secondary parkinsonism (vascular, toxic, including drug-induced), leading to diagnostic errors in 20–25% of cases. This challenge underscores the critical need for implementing reliable neuroimaging methods capable of confirming presynaptic nigrostriatal dopaminergic deficits [2, 4, 5].

The primary goal of neuroimaging, particularly magnetic resonance imaging (MRI), is to rule out other conditions that may mimic the clinical presentation of idiopathic PD. MRI and computed tomography (CT) protocols used in routine clinical practice aim to detect changes characteristic of secondary or atypical parkinsonism; however, they cannot confirm the presence of characteristic changes for PD [2].

A key limitation of standard structural neuroimaging methods is their inability to visualize the primary pathomorphological PD substrate —the progressive loss of dopaminergic neurons in the pars compacta of the substantia nigra. This dissociation between clinical and imaging features creates significant challenges because clinical signs are already present while structural imaging methods fail to provide direct diagnostic confirmation [3, 6].

Research is underway to develop and validate advanced MRI techniques with potential for visualizing more specific PD-related changes. These include, for example, neuromelanin-sensitive MRI for assessing the substantia nigra and visualizing nigrosome-1. However, to date, these techniques remain primarily research tools and are not widely used in clinical practice due to implementation challenges and reproducibility issues [2, 3].

Therefore, functional neuroimaging modalities play a crucial role in diagnosing neurodegenerative diseases. Positron emission tomography (PET) combined with brain CT using the radiotracer 6-[¹⁸F]-fluoro-L-3,4-dihydroxyphenylalanine (¹⁸F-DOPA) serves as a key functional neuroimaging method for assessing the integrity of the presynaptic dopaminergic system, which is selectively affected in PD. ¹⁸F-DOPA is a fluorinated analog of levodopa — the metabolic precursor of dopamine. Following intravenous administration, this tracer accumulates in the presynaptic terminals of nigrostriatal neurons, where it is converted into ¹⁸F-dopamine via the enzyme aromatic L-amino acid decarboxylase and stored in vesicles. Thus, PET imaging of ¹⁸F-DOPA distribution evaluates neurons’ capacity to synthesize and uptake dopamine, reflecting the status of presynaptic dopaminergic terminals. ¹⁸F-DOPA was among the first radiotracers developed for neurology. The ability to visualize brain dopaminergic structures using this radiotracer was first demonstrated in the early 1980s. In 1983, a seminal study by E.S. Garnett et al. published in Nature demonstrated ¹⁸F-DOPA accumulation in human basal ganglia, thereby enabling in vivo visualization of the dopaminergic system [7].

To reiterate, the pathogenetic basis of PD is progressive degeneration of dopamine-producing neurons in the substantia nigra, leading to striatal denervation. This morphofunctional impairment manifests as a significant reduction in the ability to uptake and accumulate ¹⁸F-FDOPA. PET quantifies the degree of this reduction, enabling both visualization and quantitative assessment of dopaminergic deficits. The most typical feature of PD is asymmetric reduction in tracer uptake, most pronounced in the posterior putamen [3].

This modality demonstrates high diagnostic accuracy, allowing differentiation of PD from conditions without presynaptic dopaminergic deficits such as essential tremor, drug-induced parkinsonism, or psychogenic parkinsonism where ¹⁸F-DOPA accumulation remains within normal limits [8].

Materials and Methods

Study design

We conducted a retrospective analysis of a case series. The study included data from 5 patients with an established clinical diagnosis of PD who underwent brain PET/CT with ¹⁸F-FDOPA (Table 1).

 

Table 1. Patient characteristics

Parameter	Patient 1	Patient 2	Patient 3	Patient 4	Patient 5
Sex	Female	Female	Male	Male	Female
Age, years	60	51	38	46	44
Disease duration, years	6	27	4	1	2
Hoehn–Yahr stage	3	3	3	1	1.5
Lateralization	Right side	Left side	Left side	Right side	Left side
Phenotype	Mixed	Akinetic-rigid (PRKN-associated mutation)	Mixed	Akinetic-rigid	Akinetic-rigid with hemidystonia
LEDD, mg/day	990	1200	950	600	475

 

PET scanograms of patients with PD.

1–5: patient numbers; N: normal.

 

¹⁸F-DOPA was used as the radiopharmaceutical. The mean activity at injection was ≈ 185 MBq. The agent was administered intravenously as a bolus into a peripheral vein. After administration, an accumulation interval of approximately 80 minutes was maintained. Scanning time was 15 minutes per table position. Matrix size was 256 × 256, voxel size 1.95 × 1.95 × 3.27 mm.

PET/CT scanning was performed at the PET-Technology Center of Nuclear Medicine at Sechenov University using a hybrid PET/CT scanner GE Discovery 710 (GE Medical Systems). Instrument calibration and quality control were performed daily according to the EARL2 protocol (EANM Research Ltd.). The CT portion of the study included standard brain imaging in the axial plane with slice thickness of 1.3 mm, matrix 512 × 512, tube voltage 120 kV and tube current-time product 10–300 mAs.

Additionally, the scanning included a CT series for attenuation correction.

Image reconstruction was performed with a matrix of 256 × 256 and slice thickness of 3.27 mm. The standardized uptake value calculation method was SUVbw (body weight).

Assessment of results

Signs of reduced tracer uptake were assessed by a radiologist. In addition to visual assessment of ¹⁸F-DOPA metabolism asymmetry in the brain dopaminergic structures, a quantitative evaluation of radiotracer uptake in the anterior and posterior putamen relative to uptake in the cerebellar gray matter (SUVr) was also performed.

Results

The study results in the form of PET scanograms are presented in the Figure and summarized in Table 2.

 

Table 2. PET scanning results in patients

Patient number	SUVr in the putamen				Radiologist’s assessment
	anterior segments		posterior segments
	right	left	right	left
1	2.87	2.43	2.92	2.06	Significant reduction in radiopharmaceutical uptake in the posterior left putamen, with no hypometabolism noted on the right side
2	1.64	1.47	1.38	1.30	Pronounced, relatively symmetric reduction in radiopharmaceutical uptake in the putamen with slight left-sided predominance
3	2.10	2.11	1.44	1.54	Mildly asymmetric (more pronounced on the right) significant reduction in radiopharmaceutical uptake in the bilateral putamen
4	2.16	1.97	1.69	1.32	Moderate reduction in radiopharmaceutical uptake in the right putamen and marked reduction in the left
5	2.05	2.08	1.67	1.82	Marked reduction in radiopharmaceutical uptake bilaterally, with slight asymmetry toward the right putamen
Normal value	3.04	2.97	2.98	2.98	No evidence of reduced radiopharmaceutical uptake in the bilateral putamen was noted

 

Discussion

The results obtained in this study convincingly demonstrate the key role of ¹⁸F-DOPA PET in objectively quantifying dopaminergic deficits, which represent a pathognomonic PD sign. In all clinical cases included in the analysis, significantly reduced radiotracer uptake was observed in the putamen compared to values in healthy individuals. This finding directly reflects the pathophysiological basis of the disease — progressive degeneration of dopaminergic neurons in the pars compacta of the substantia nigra and subsequent degeneration of their terminals in the striatum. The reduction in SUVr values is a direct consequence of impaired presynaptic function, specifically decreased activity of aromatic L-amino acid decarboxylase, which converts ¹⁸F-DOPA to ¹⁸F-dopamine for vesicular storage [5, 9, 10].

Of particular diagnostic value is not only the reduction in radiotracer uptake itself but also its specific spatial pattern. Consistent with literature reports, PD is characterized by a posterior-to-anterior gradient of involvement, which was observed in all examined patients.

This phenomenon has a clear pathomorphological basis: neurodegeneration in the substantia nigra begins in the ventrolateral portion and spreads mediodorsally, corresponding to projections to the posterior and then anterior parts of the putamen. It is precisely this gradient that allows for high-confidence differentiation of PD from atypical parkinsonian syndromes (e.g., multiple system atrophy or progressive supranuclear palsy), which are characterized by more diffuse and symmetric involvement of the striatum, often with involvement of the caudate nucleus [3, 5, 10].

Another critically important marker of PD, confirmed in our study, is the asymmetry of nigrostriatal degeneration. In all patients, asymmetric reduction in radiopharmaceutical uptake between the left and right hemispheres was observed. This asymmetry at the neurochemical level directly correlates with the classic clinical presentation of PD, which almost invariably debuts with unilateral motor symptoms. The side with more pronounced SUVr reduction is typically contralateral to the side exhibiting primary or more severe clinical symptoms. Thus, ¹⁸F-DOPA PET provides objective confirmation of clinical observations [8, 11].

Of particular interest are the results in patient 2 with a PRKN gene mutation: marked, nearly symmetric reduction in radiopharmaceutical uptake in the putamen. These findings align well with literature data for this genetic form of the disease [12].

The study results underscore the indispensability of ¹⁸F-DOPA PET for addressing complex diagnostic challenges. Clinical diagnosis of PD can be difficult in early stages, with diagnostic accuracy even by experienced neurologists not exceeding 80–85%. PET enables detection of dopaminergic deficits at the preclinical or earliest clinical stage, when neuronal loss has already reached a critical threshold (50–70%), but motor symptoms remain nonspecific or minimally expressed. This opens a window for potentially early initiation of neuroprotective therapy in the future.

In the context of differential diagnosis, ¹⁸F-DOPA PET serves as the gold standard for distinguishing PD from mimicking conditions of different etiology, primarily essential tremor, where the dopaminergic system remains intact and scan results fall within normal limits. This method is also effective for differentiating PD from drug-induced, vascular, and psychogenic (functional) parkinsonism.

The obtained data confirm that brain ¹⁸F-DOPA PET/CT is a highly sensitive and specific method providing an objective quantitative biomarker of the dopaminergic system state. Characteristic patterns of reduced radiopharmaceutical uptake — asymmetry and posterior-anterior gradient — are reliable indicators of nigrostriatal degeneration and serve as key tools for early and accurate PD diagnosis verification, disease progression monitoring, and therapeutic intervention efficacy assessment in research setting.

About the authors

Sergey N. Illarioshkin

Russian Center of Neurology and Neurosciences; The Russian University of Medicine

Email: annaly-nevrologii@neurology.ru
ORCID iD: 0000-0002-2704-6282

Dr. Sci. (Med.), Professor, Full Member of RAS, Director, Brain Institute, Deputy Director for Science, Head, Neurology departmen

Russian Federation, Moscow; Moscow

Maksim N. Andreev

Russian Center of Neurology and Neurosciences; Federal Scientific and Clinical Center for Medical Rehabilitation and Balneology

Author for correspondence.
Email: annaly-nevrologii@neurology.ru
ORCID iD: 0000-0002-3718-6238

Cand. Sci. (Med.), neurologist, Consulting and diagnostic department, Institute of Clinical and Preventive Neurology, Federal Treatment and Rehabilitation Center in Moscow

Russian Federation, Moscow; Moscow

Alina A. Liaskovik

Russian Center of Neurology and Neurosciences; Federal Network of Nuclear Medicine Centers PET-Technology

Email: annaly-nevrologii@neurology.ru
ORCID iD: 0000-0001-8062-0784

radiologist, Radiology department, Institute of Clinical and Preventive Neurology, radiologist, “PET-Technology” Oncoradiological Center

Russian Federation, Moscow; Moscow

Maksim Yu. Krasnov

Russian Center of Neurology and Neurosciences

Email: annaly-nevrologii@neurology.ru
ORCID iD: 0000-0002-5321-3451

Cand. Sci. (Med.), neurologist, Consulting and diagnostic department, Institute of Clinical and Preventive Neurology

Russian Federation, Moscow

Ekaterina Yu. Fedotova

Russian Center of Neurology and Neurosciences

Email: annaly-nevrologii@neurology.ru
ORCID iD: 0000-0001-8070-7644

Dr. Sci. (Med.), Head, 5^th Neurological department, Institute of Clinical and Preventive Neurology

Russian Federation, Moscow

Sergey Yu. Dvoynikov

Federal Network of Nuclear Medicine Centers PET-Technology

Email: annaly-nevrologii@neurology.ru
ORCID iD: 0009-0002-0664-8310

General Director, LLC “PET-Technology Balashikha”

Russian Federation, Moscow

Larisa M. Tulina

Federal Network of Nuclear Medicine Centers PET-Technology; I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: annaly-nevrologii@neurology.ru
ORCID iD: 0000-0002-9148-2046

chief physician, Nuclear Medicine Center on Bolshaya Pirogovskaya, Associate Professor, Department of pharmacology, Nelyubin Institute of Pharmacy

Russian Federation, Moscow; Moscow

Alexander E. Nikolaev

Federal Network of Nuclear Medicine Centers PET-Technology

Email: annaly-nevrologii@neurology.ru
ORCID iD: 0000-0001-5151-4579

chief radiologist

Russian Federation, Moscow

Anton V. Tyurin

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: annaly-nevrologii@neurology.ru
ORCID iD: 0009-0000-3626-5578

radiologist, Head, Remote reporting center

Russian Federation, Moscow

References

Supplementary files