Brain [¹⁸F]FDG PET/CT in Clinical Practice: Indications, Methodological Considerations and Metabolic Patterns

INTRODUCTION

Glucose accounts for up to 95% of ATP production required to sustain neuronal and synaptic function. [18F]FDG – a radiolabeled glucose analog – serves as an indicator of neurosynaptic activity and neuronal density, enabling in vivo quantification of regional cerebral glucose metabolism. Resembling endogenous glucose, intracellular accumulation of [18F]FDG depends on the integrity of glucose transporters, hexokinase availability, and astrocyte-neuron metabolic dynamics[1, 2].

Physiologically, [18F]FDG uptake is greater in regions characterized by high baseline synaptic and functional activity – such as the basal ganglia, frontal eye fields, posterior cingulate cortex, and visual cortex- and lower in areas with reduced resting metabolic demand – such as the medial temporal cortex[3]. Notably, [18F]FDG PET imaging in control populations has demonstrated region-specific ageassociated declines in cerebral glucose metabolism, primarily involving the anterior cingulate, frontolateral cortex, and perisylvian regions[4].

Leveraging the neurometabolic coupling between cerebral activity and metabolic demand, alterations in [18F]FDG uptake can exemplify abnormal functional patterns before morphologic presentation is seen on CT and MRI scans.

CLINICAL INDICATIONS

Cognitive Impairment and Dementia

Neurodegenerative dementias are usually preceded by a prodromal phase – mild cognitive impairment (MCI) – characterized by subtle clinical-neuropsychological changes that do not yet interfere with daily life activities. Related to synaptic dysfunction and long-lasting pathological deposition of toxic proteins in the brain, M

Within the A/T/N framework of Alzheimer’s disease biomarkers – amyloid (A), tau (T), and neurodegeneration (N) – [¹⁸F]FDG PET serves as a well-established marker of neurodegeneration and disease progression. It independently predicts conversion from mild cognitive impairment (MCI) to AD, irrespective of hippocampal volume or amyloid status. [¹⁸F]FDG PET complements amyloid and tau biomarkers, whether derived from cerebrospinal fluid analysis or PET imaging, and is recommended to support early diagnosis of Alzheimer’s disease (AD) in mild cognitive impairment (MCI), Lewy body dementia (DLB), and frontotemporal lobar degeneration (FTLD). Furthermore, [¹⁸F]FDG PET aids in differentiating AD from FTLD, DLB, vascular dementia, and atypical Parkinsonian syndromes associated with cognitive decline, particularly when clinical evaluation and MRI are inconclusive. Consensus algorithms now endorse [¹⁸F]FDG PET as a first-line tool when non-AD etiologies are suspected. Characteristic topographic hypometabolic patterns have been described for AD, FTLD, and DLB, with spatial patterns correlating strongly with clinical phenotypes. Importantly, a normal [¹⁸F]FDG PET scan at the MCI stage has a high negative predictive value, with fewer than 10% of patients progressing to dementia three years[1, 5-8].

Movement Disorders

[¹⁸F]FDG PET supports the differentiation of Parkinson’s disease (PD) from atypical Parkinsonian syndromes (APS) – including multiple system atrophy (MSA), progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and dementia with Lewy bodies (DLB). [¹⁸F]FDG PET is also useful in imaging prodromal α-synucleinopathies, such as idiopathic REM sleep behavior disorder, where metabolic patterns partially overlap with PD and related disorders[1, 6, 9, 10].

The clinical utility of [¹⁸F]FDG PET extends to several motor neurodegenerative disorders beyond Parkinsonian syndromes, notably amyotrophic lateral sclerosis (ALS) and Huntington’s disease (HD). In ALS, [¹⁸F]FDG PET is primarily employed to evaluate extra-motor cortical involvement and to better characterize patients within the ALS–frontotemporal dementia spectrum. As extensive frontotemporal involvement is associated with a more aggressive clinical course, [¹⁸F]FDG PET may also be useful for prognostic assessment in ALS. In HD, [¹⁸F]FDG PET can assist in differentiating early psychiatric or behavioral manifestations from other neurodegenerative disorders with overlapping clinical features. Notably, presymptomatic carriers of pathogenic Huntington’s mutations may exhibit region-specific metabolic alterations detectable by [¹⁸F]FDG PET well before the onset of motor symptoms[1, 6, 11].

Epilepsy

The primary objective of [¹⁸F]FDG PET in this setting is to localize the epileptogenic zone (EZ), thereby guiding surgical planning when conventional imaging modalities (such as MRI) are inconclusive or when multiple structural lesions are present. Interictally, epileptogenic foci typically manifest as hypometabolic regions that may extend beyond the seizure onset zone, reflecting both primary pathology and propagation networks. This finding reflects underlying neuronal dysfunction and uncoupling between cerebral glucose metabolism and blood flow, which is frequently observed in epilepsy.

In MRI-negative epilepsy, [¹⁸F]FDG PET can uncover hypometabolic regions not visible on structural imaging. These findings may direct the placement of intracranial electrodes for invasive electroencephalographic monitoring and improve overall surgical strategy. Notably, patients with negative MRI but positive PET findings demonstrate postoperative seizure-free rates comparable to those with clear structural lesions.

In extratemporal lobe epilepsy, the detection rate of the EZ is comparatively lower (38–67%) than that observed in temporal lobe epilepsy (~80%); nevertheless, the technique remains clinically valuable, especially for identifying subtle cortical malformations such as focal cortical dysplasia. While the examination is conventionally performed during the interictal period to detect hypometabolism, ictal [¹⁸F]FDG administration – although rare – can highlight hypermetabolic foci corresponding to seizure onset. [¹⁸F]FDG PET/CT offers strong prognostic value, with a more restricted pattern of hypometabolism predicting better postsurgical seizure control and cognitive outcomes[1, 12-15].

Neurooncology

Increased [¹⁸F]FDG uptake on PET images reflects the intense glycolytic activity of neoplastic cells, aiding detection of certain viable tumor tissue. Physiologically high glucose metabolism in cortical gray matter and nonspecific [¹⁸F]FDG uptake in inflammatory lesions limit tumor-to-background contrast and reduce sensitivity compared to amino acid PET tracers, which are preferred when available. Systematic employment of whole-body [¹⁸F]FDG PET/CT is of limited value for detecting unsuspected cerebral metastases in cancer patients.

In primary central nervous system lymphoma (PCNSL), [¹⁸F]FDG PET demonstrates consistently high and homogeneous tracer accumulation. This allows reliable differentiation from non-neoplastic processes such as opportunistic infections in immunocompromised patients. Pooled sensitivity and specificity have been reported to exceed 84%, with baseline uptake intensity correlating with both therapeutic response and overall prognosis. Whole-body [¹⁸F]FDG PET is additionally used for staging, with extracranial lymphoma detection characterized by low false-positive rates.

In gliomas, [¹⁸F]FDG PET has a limited role due to substantial overlap between low-grade tumor uptake and that of normal white matter, as well as potential uptake in inflammatory tissue. Nevertheless, when amino acid tracers are not available, [¹⁸F]FDG PET may be used in initial tumor characterization, with increased uptake generally associated with higher histologic grade and poorer prognosis. Follow-up studies can also assist in detecting malignant transformation and provide prognostic information at recurrence. Post-treatment imaging represents another indication. [¹⁸F]FDG PET/CT can help distinguish recurrent tumor from radiation necrosis, typically performed no earlier than 6–8 weeks after radiotherapy, with reported sensitivity and specificity of approximately 84%[1, 16-18].

Cerebral Infectious and Inflammatory Diseases

Brain [¹⁸F]FDG PET offers valuable insights in various cerebral infectious diseases, primarily aiding in differential diagnosis, while assessing disease activity. In evaluating alveolar echinococcosis (AE), strong correlations have been observed between Echinococcus serology and [¹⁸F]FDG tracer uptake. [18F]FDG PET can analyze immune cell activity at the parasite-host interface, assessing disease progression and treatment response. This is critical for guiding treatment intensity in inoperable patients and appraising the safety of structured treatment interruptions. In immunocompromised individuals, [18F]FDG PET/CT can assist in distinguishing between cerebral toxoplasmosis and CNS lymphoma, which may present similar MRI patterns. For rare CNS infections, [18F]FDG PET/CT has correctly identified unusual cases, such as suppurative meningomyelitis and ventriculitis. While their low incidence limits prospective studies, these findings can have clinical value by guiding treatment changes and improving outcomes, especially in patients with unexplained fever and neurological signs[19-21].

Autoimmune encephalitis (AIE) represents the primary inflammatory indication for cerebral [¹⁸F]FDG PET. Displaying higher sensitivity compared to MRI – particularly in N-methyl-D-aspartate receptor (NMDAR) encephalitis – [¹⁸F]FDG PET is particularly relevant when MRI findings are negative or inconclusive. While aiding early diagnosis, this hybrid imaging technique can also help evaluate therapeutic efficacy on follow-up scans. Beyond AIE, [¹⁸F]FDG PET provides diagnostic support in neurosarcoidosis, enabling visualization of both cerebral granulomatous lesions and extra-neural manifestations – even without corresponding MRI abnormalities – particularly when CNS biopsy is difficult. In neuropsychiatric systemic lupus erythematosus (NPSLE), while MRI detects macrovascular damage, [¹⁸F]FDG PET can reveal alterations related to microvascular damage and antibody-mediated injury undetectable on MRI. Employed to evaluate post-COVID-19 (neuro-COVID) sequelae, [¹⁸F]FDG PET allows for the assessment of specific neuronal impairments and time-dependent metabolic alterations at an individual level. The severity of its distinct hypometabolic pattern correlates with cognitive and neuropsychiatric deficits[1, 21, 22].

CONTRAINDICATIONS AND CAUTIONS

• Uncontrolled hyperglycemia – blood glucose levels above 150 mg/dL (~8.3mmol/L) can significantly reduce cerebral [¹⁸F]FDG uptake through increased competition between elevated plasma glucose and FDG for GLUT transporters and hexokinase; stochastic noise would also be enhanced, further degrading lesion-to-background contrast.
• Pregnancy – judicious clinical judgment is imperative to determine whether anticipated benefits sufficiently outweigh potential risks of harm.
• Breastfeeding – mothers should interrupt breastfeeding for 24h following PET examination.
• Recent seizure activity – interictal scans performed less than 24 hours after the last seizure can lead to transient perfusion and metabolic changes, challenging interpretation.
• Inability to remain still during image acquisition (30-60 minutes) – leads to blurring of tracer activity across cerebral structures, resulting in a significant decrease of spatial resolution, thus rendering image interpretation challenging, if not entirely unfeasible.
• Lack of cooperation [1, 2, 6, 23].

PROCEDURE AND PATIENT PREPARATION

Patients should fast for 4-6 hours prior to the injection, though encouraged to maintain hydration with water, for serum glucose levels not interfere with cerebral [¹⁸F]FDG uptake. Parenteral feeding or intravenous fluid containing dextrose should also be withheld for 4-6 hours before injection, for the same reason. Also, caffeine, alcohol and other drugs that may affect cerebral glucose metabolism should be avoided on the day of the PET examination. Medication for diabetes does not need to be discontinued on the day. It is preferred to schedule the study 4-6 weeks after radiation therapy, where appropriate.

The patient must be exposed to external stimuli as little as possible, before and after [¹⁸F]FDG injection. The cannula for intravenous administration should be placed at least 10 minutes before the [¹⁸F]FDG. Patients should be resting in a quiet and dimly lit room with their eyes open, without speaking, reading, or engaging in major movements or anything cognitively challenging, several minutes before [¹⁸F]FDG administration as well as during the uptake phase of [¹⁸F]FDG, which lasts around 20 minutes. Before the scanning procedure is started, patients should void their bladders for maximum comfort during the study. It is recommended that the patient void the bladder again after the scan in order to minimize radiation exposure. If sedation is necessary, it is recommended to be done as late as possible, at least 20 minutes after the [¹⁸F]FDG injection. For preoperative evaluation of epilepsy, a continuous EEG recording is required. Monitoring should start before injection (ideally 2 hours before) in order to ensure that [¹⁸F]FDG is not administered in a postictal situation, and should be maintained at least until 20 min after injection[1, 2, 6, 23].

MEDICAL INFORMATION NECESSARY FOR AN ACCURATE PROCEDURE AND INTERPRETATION

• Patient identification and demographics (age, sex, handedness, body weight, height)
• Primary diagnosis and specific clinical indication for the PET/CT study
• History of neurological and psychiatric disorders, as well as past surgery, trauma or radiation to the brain
• History of diabetes and fasting status.
• Current neurological and psychiatric status and relevant symptoms.
• Current and recent medications, particularly those influencing cerebral metabolism (e.g., benzodiazepines, antiepileptics, neuroleptics, corticosteroids, levodopa, insulin).
• Prior structural neuroimaging (CT, MRI) and functional brain examinations (EEG).
• The patient’s ability to lie still for 30 minutes to 1h. If sedation is necessary, [¹⁸F]FDG should be administered prior to it[1, 2, 6].

INTERPRETATION

Acquisition images should first be carefully checked for movement or attenuation artefacts, as well as possible misalignments of the head. Knowledge of normal glucose brain metabolism variations, especially age-dependent changes, as well as medication-related changes, is mandatory for accurate interpretation and reporting. A normal database should be available, preferably obtained with the same type of camera, under the same acquisition circumstances and using the same type of reconstruction and attenuation correction. Matching spatial resolution is the most important parameter needed for optimal database use. This allows assessment of normal variability of regional [¹⁸F]FDG uptake and improves diagnostic accuracy[1, 2].

Cognitive Impairment and Dementia

Different neurodegenerative diseases preferentially involve distinct brain regions, resulting in reproducible [¹⁸F]FDG PET uptake patterns that can now be quantitatively assessed through statistical mapping technologies. Differentiating AD, FTLD, and DLB with [¹⁸F]FDG PET has become standard practice. As the nosology of FTLD evolves, encompassing behavioral variant FTD, the three clinical subtypes of primary progressive aphasia, and movement disorders such as progressive supranuclear palsy and corticobasal degeneration, disease-specific metabolic signatures have been delineated. The recognition of mixed dementias and coexisting pathologies, particularly in the elderly, has shifted interpretation from a binary AD versus non-AD framework toward identifying the predominant pathology most consistent with clinical presentation[1, 6, 8].

In Alzheimer’s disease, hypometabolism is typically observed in the parietotemporal and posterior cingulate cortex – and, with disease progression, in the frontal lobe and hippocampus – while the primary sensorimotor and primary visual cortices, striatum, thalamus, pons, and cerebellum are usually spared. Notably, reductions in glucose metabolism often exceed the degree of structural atrophy observed in most affected brain regions, with the exception of the hippocampus. This discrepancy suggests the existence of synaptic compensatory mechanisms that sustain neuronal activity despite ongoing tissue damage, particularly in younger patients. However, hippocampal hypometabolism becomes more prominent in late-onset AD. Although frontal hypometabolism is also commonly associated with advanced stages of AD, frontal lobe involvement can be distinguished early in a fraction of patients with prominent behavioral symptoms (behavioral variant of AD [bvAD]), thus challenging differential diagnosis. Remarkably, frontal lobe metabolic impairment has been more frequently reported in female patients with AD suspicion, compared to their male counterparts. AD subtypes with visual symptoms (posterior cortical atrophy) show distinct bilateral occipitoparietal hypometabolism. The logopenic variant of primary progressive aphasia (lvPPA) shows decreased [¹⁸F]FDG uptake typically in the posterior temporal cortex and inferior parietal lobule, with the left hemisphere often more severely affected, which is similar to AD findings and often reflects underlying AD pathology. Posterior cortical atrophy (PCA) – an atypical variant of AD – is characterized by often asymmetric parietotemporal and occipital hypometabolism, the latter aiding differentiation from typical AD[1, 5, 7, 8, 24, 25].

Lewy body dementia (DLB) and Alzheimer’s disease have a similar hypometabolic cerebral distribution with marked decreases in association cortices and relative sparing of subcortical structures and primary somatomotor cortex. However, metabolic reduction in the occipital cortex is the key feature of supporting the diagnosis of DLB, often described as the “occipital tunnel” sign. Additional differentiating characteristics of DLB versus AD include relatively preserved metabolism in the posterior cingulate gyrus (compared with the precuneus) – “cingulate island” sign – as well as generally preserved hippocampal [¹⁸F]FDG uptake. Crossed cerebellar diaschisis (CCD) may accompany posterior cortical hypometabolism due to deactivation of cortico-ponto-cerebellar projections. While CCD occurs across neurodegenerative syndromes and is reported most frequently in corticobasal syndrome and primary progressive aphasia, isolated reports document CCD in DLB as well. Accordingly, cerebellar hypometabolism on FDG PET should be interpreted as a non-specific remote effect, integrated with the characteristic DLB pattern (occipital hypometabolism with cingulate-island sign) and clinical data[6-8, 24, 26, 27].

Frontotemporal degeneration (FTLD) encompasses the behavioral variant frontotemporal dementia (bvFTD), the primary progressive aphasia (PPA) spectrum (semantic, non-fluent/agrammatic, and logopenic variants), and FTLD-spectrum movement disorders (e.g., corticobasal syndrome, progressive supranuclear palsy). The canonical pattern of behavioral variant FTD (bvFTD) shows hypometabolism in the frontal association cortices (dorsolateral, medial and orbitofrontal), and the anterior temporal lobes, with progressive involvement of the caudate nuclei and thalami. The bilaterally involved frontomedial cortex of bvFTD is typically well demarcated – a feature originally described on CT and MRI as “lobar atrophy”. In semantic variant PPA (svPPA), [¹⁸F]FDG uptake typically demonstrates asymmetric anterior temporal hypometabolism, most often with left-predominant – reflecting languagedominant hemisphere involvement. The nonfluent variant of PPA (nfvPPA) is often associated with hypometabolism affecting the left posterolateral frontal and superior medial frontal cortices, and inferofrontal regions (insula). In logopenic variant PPA (lvPPA), [¹⁸F]FDG PET typically reveals asymmetric hypometabolism of the left posterior perisylvian cortex (posterotemporal and inferoparietal lobes), a pattern that aids differentiation from svPPA and nfvPPA and supports its frequent association with underlying AD pathology. In corticobasal syndrome (CBS), hypometabolism often involves the frontoparietal cortex, basal ganglia, and thalamus, often most pronounced in the hemisphere contralateral to the clinically predominant symptoms. The characteristic [¹⁸F]FDG uptake pattern of progressive supranuclear palsy (PSP) typically involves the medial frontal cortex, anterior cingulate, and midbrain, frequently extending to the thalamus and basal ganglia[6-8, 24, 25].

Vascular dementias show no signature patterns of cortical hypometabolism; uptake abnormalities mirror the topography of vascular injury and its remote network effects – including crossed cerebellar diaschisis after supratentorial infarction. These changes are often heterogeneous and multifocal, often asymmetric across cortical and subcortical territories – although they may appear more symmetric in diffuse small-vessel disease. Particularly in older patients, vascular dementia frequently coexists with other neurodegenerative pathologies – most commonly Alzheimer’s disease – in what is termed “mixed dementia”. Interpretative cues, in a top-down approach, include the absence of expected neurodegenerative patterns (e.g., parietal hypometabolism with preserved precuneus) or, conversely, an atypical pattern such as precuneus involvement with relative sparing of the temporal lobes[1, 2, 8, 25].

Movement Disorders

At first glance, brain [¹⁸F]FDG PET scans in Parkinson’s disease (PD) often appear unremarkable. On closer inspection – particularly using voxel-based statistical mapping – PD shows posterior temporo-parietal and occipital hypometabolism, sometimes extending to the frontal lobes in patients with cognitive impairment. In parallel, there is relative hypermetabolism of the basal ganglia (putamen and pallidum), thalamus, sensorimotor cortex, pons, and cerebellum; this network expression can be attenuated under dopaminergic treatment. Unlike the striatal hypometabolism characteristic of atypical parkinsonian syndromes (APS), patients with PD usually show preserved or relatively increased [¹⁸F]FDG uptake, compared with cortical regions. This reflects compensatory activity in the striatopallidal-thalamic circuit in the setting of nigrostriatal degeneration.

By contrast, multiple system atrophy (MSA) is associated with bilateral reductions in putaminal uptake, progressive supranuclear palsy (PSP) most often demonstrates caudate hypometabolism, and corticobasal syndrome (BCS) typically displays asymmetric striatal reductions accompanied by concordant cortical asymmetry. MSA is characterized by hypometabolism involving the (posterior) putamen, pons and cerebellum. The pattern of [¹⁸F]FDG uptake reduction in MSA varies with the clinical subtype: in MSA with predominant parkinsonism (MSA-P), changes are more pronounced in the striatum, whereas in the cerebellar variant (MSA-C), hypometabolism is more prominent within the pontocerebellar structures. PSP displays consistent regional hypometabolism in the medial, dorsal, and ventrolateral frontal areas – including the anterior cingulate gyrus, supplementary motor area, precentral gyrus, and premotor–to–posterior prefrontal areas – with additional involvement of the caudate, thalamus and upper brainstem. A distinct focal decrease in midbrain [¹⁸F]FDG uptake can also be observed, sometimes preceding MRI-detectable midbrain tegmental atrophy (the “Hummingbird sign”). CBS is distinguished by asymmetric striatal hypometabolism, with concordant cortical asymmetry, usually affecting the frontoparietal regions[1, 6, 8, 10, 12, 28].

In amyotrophic lateral sclerosis (ALS), [¹⁸F]FDG PET typically demonstrates hypometabolism involving the primary motor, premotor and supplementary motor cortices, with extension into the frontoparietal regions. Conversely, relative hypermetabolism is often observed in the medial temporal cortex, cerebellum, and brainstem. ALS exists in a continuum with frontotemporal dementia, as up to half of patients show subtle cognitive or behavioral impairment, while approximately 10-15% fulfil criteria for overt frontotemporal dementia[1, 6, 8]. Huntington’s disease has a well-described, characteristic neuroimaging finding: severely reduced [¹⁸F]FDG uptake in the bilateral striatum. Beyond this core finding, patients also exhibit widespread cortical hypometabolism as well as increased thalamic, occipital, and cerebellar metabolism. Wilson’s disease has also shown a decreased striatal uptake, mainly in the caudate nucleus and in the lenticular nuclei, while the cortical glucose metabolism often remains normal [1, 2, 6, 8, 11].

Epilepsy

In the interictal phase, [¹⁸F]FDG PET typically demonstrates hypometabolism in the seizure onset zone (SOZ) and propagation zones, which may extend across the entire irritative zone. A global reduction of grey matter metabolism relative to controls has also been reported, attributable to mechanisms including neuronal loss, reduced synaptic density, vascular changes, or post-ictal depression. In temporal lobe epilepsy (TLE), hypometabolism often extends beyond the presumed epileptogenic zone, consistent with the concept of epileptogenic and propagation networks. Prefrontal asymmetry correlates with mild cognitive impairment, whereas bitemporal hypometabolism is associated with memory deficits and increased risk of postoperative decline. In extratemporal lobe epilepsy (ETLE), focal hypometabolism is a strong predictor of postoperative seizure freedom. Although hypometabolism is the predominant finding, interictal hypermetabolic cortical or subcortical foci may occur, reflecting hypermetabolic cortical or subcortical foci may occur, reflecting pathological hyperactivity or activated inhibitory circuits.

In children and adolescents, where etiologies are diverse (tumors, birth-related lesions, malformations of cortical development), [¹⁸F]FDG PET is especially valuable. Lesions typically present as hypometabolic, often exceeding the extent visible on MRI, and PET may reveal abnormalities in MRI-negative or equivocal cases – particularly in focal cortical dysplasia type II. It is essential for evaluating multilobar, drug-resistant foci, guiding complete resection and surgical outcomes, especially in hemispherectomy. In specific epilepsy syndromes, [¹⁸F]FDG PET can localize the epileptogenic tuber in tuberous sclerosis complex (typically as hypometabolism exceeding MRI abnormalities), reveal predominantly hypometabolism changes in Sturge-Weber syndrome (with cortical hypermetabolism in young children signaling severe disease requiring early surgery), demonstrate heterogenous uptake patterns in Lennox-Gastaut syndrome where focal hypometabolism may guide surgical planning, assess contralateral hemispheric integrity and cognitive prognosis in hemimegalencephaly, and detect early metabolic abnormalities in Rasmussen encephalitis – both hypo- and hypermetabolism – thereby supporting diagnosis when MRI is inconclusive and excluding bilateral involvement. Pediatric interpretation is challenging given age-dependent normal uptake patterns, underscoring the importance of software-based quantification against age-matched controls. FDG PET usually reveals asymmetric hypometabolism, but the abnormality often exceeds the true ictal onset zone, making it more reliable for identifying laterality and lobar localization rather than the precise seizure focus[1, 6, 12, 14].

Neurooncology

[¹⁸F]FDG PET is an established diagnostic tool in oncologic imaging due to its ability to evaluate lesions based on glucose metabolism activity. It provides valuable information in differentiating between common enhancing malignant brain tumors (e.g., high and low grade gliomas), metastatic brain tumors and primary central nervous system lymphoma (PCNSL). Semi-quantitative measures like Standardized Uptake Value (SUV) and Tumor-to-Background Ratios (TBR) are useful, while SUVmax is reported as the main interpreting tool, with corresponding values from highest to lowest, in order: PCNSL > metastatic brain tumors > high-grade gliomas > low-grade gliomas. However, its impact can be limited in brain imaging compared to amino-acid PET due to the high physiological uptake of [¹⁸F]FDG in normal brain gray matter and variable uptake by inflammatory lesions. Delayed acquisitions (typically 3-5 hours post-injection) are often proposed to increase the tumor-to-healthy brain uptake ratio, which can be particularly beneficial for differentiating recurrence from post-treatment necrosis. Brain metastases arising from primary tumors with low [¹⁸F]FDG uptake – such as mucinous adenocarcinoma, lobular breast carcinoma, and renal cell carcinoma – should generally not be evaluated with this tracer, although a focal hypometabolic area may occasionally indicate a large metastatic lesion[1, 6, 17, 29, 30].

Cerebral Infectious and Inflammatory Diseases

While the high physiological glucose uptake in normal brain gray matter can sometimes limit contrast between lesions and healthy tissue, particularly when compared to amino-acid PET in some conditions, [¹⁸F]FDG PET/CT has demonstrated clinical utility across a spectrum of these disorders. In neurosarcoidosis, lesions typically display increased [¹⁸F]FDG uptake, sometimes preceding or exceeding MRI abnormalities. In autoimmune encephalitis (AIE), distinct patterns of regional abnormalities have been described depending on the antibody subtype: medial temporal lobe and basal ganglia hypermetabolism with parietal–occipital hypometabolism is common, with anti-LGI1 encephalitis showing preferential medial temporal and basal ganglia involvement, while anti-NMDAR encephalitis often combines occipital hypometabolism with frontal or medial temporal hypermetabolism. Suppurative meningomyelitis may be identified as increased linear uptake within the spinal canal, which normalizes after treatment, whereas ventriculitis is characterized by intense periventricular hypermetabolism even when CT is inconclusive. In HIV-positive patients, PET aids differential diagnosis between primary CNS lymphoma, which shows high focal uptake, and cerebral toxoplasmosis, which typically demonstrates low uptake. In neuropsychiatric lupus (NPSLE), striatal hypermetabolism has been frequently observed, correlating with psychiatric and motor manifestations, although cortical findings are variable and sometimes non-specific. In LongCOVID, a reproducible pattern of hypometabolism has been reported at the group level, typically involving fronto-orbital olfactory regions, (para)limbic areas, the brainstem, and cerebellum. Regional changes correlate with clinical symptoms, with frontal hypometabolism linked to concentration and mood disturbances, medial temporal changes to memory impairment, and pontine abnormalities to paresthesias. Finally, in alveolar echinococcosis, [¹⁸F]FDG PET/CT commonly demonstrates annular or irregular peripheral hypermetabolism surrounding the lesion. Uptake intensity reflects granulomatous inflammatory activity and microvascular proliferation and can therefore assist in assessing disease activity[1, 6, 19-22].

Conflicts of interest and sources of funding

The authors declare no conflict of interest. No artificial intelligence automatically generated text was inserted in this manuscript, and no image was previously published in another journal or is under consideration for publication elsewhere. This research received no external funding.

Authors’ contribution

Conceptualization M.R.M, G.S.P., A.I.B and T.S.M.; methodology, G.S.P., L.E.M.,D.M.,T.S.M.; validation, D.M., O.C.C. and O.M.S.; data curation, D.M., A.M.R., G.I.; writing— original draft preparation, G.S.P, A.I.B.,L.E.M.; writing—review and editing, M.R.M., O.C.C., G.I.; supervision, A.M.R., D.M., O.M.S.; project administration, M.R.M.; All authors have read and agreed to the published version of the manuscript.

Ethics approval and consent to participate

The study was conducted under the Declaration of Helsinki. The research was conducted under ethical guidelines and regulations, ensuring compliance with all necessary protocols.

Patient consent for publication

Not applicable

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