Several positron emission tomography (PET) radiopharmaceuticals beyond fluorodeoxyglucose (FDG) have been used to study the physiology and pathophysiology in neurosciences. This article provides a broad overview of some of the commonly studied radiopharmaceuticals for PET imaging in selected neurologic conditions, particularly attempting to study their clinical relevance. Future studies on the use of advanced PET imaging in delineating neural pathophysiology, drug development, and altering patient management and outcomes across the disciplines of neurosciences are needed.

Keywords

Positron emission tomography

Brain

Central nervous system

Positron

Dementia

Parkinson disease

Epilepsy

Neuroinflammation

Key points

Introduction

Positron emission tomography (PET) is a molecular imaging technique used for generating maps of functional and biochemical activity in target tissues in vivo.1 PET has led to significant insights into nervous system biology, physiology, and pathophysiology in health and disease. Several of these insights and applications have a direct usefulness for the neurologist.2 Although fluorine 18 [18F]fluorodeoxyglucose (FDG) has remained a workhorse of clinical PET imaging, many other radiolabeled biomolecules have been studied using PET.3 In this article, brain PET ligands beyond FDG, across the spectrum of neurologic subspecialties, including dementias, movement disorders, epilepsy, brain tumors, and neuroinflammation, are reviewed. Of the numerous available PET radiopharmaceuticals, a few have been selected that have been extensively studied in common neurologic disorders.

Dementia

There is widespread deposition of amyloid in the cerebral cortex in Alzheimer disease (AD). Carbon 11 (11C) Pittsburgh compound B (PiB) is a radiolabeled analogue of thioflavin dye, which has been established as a valid biomarker for amyloid deposition in the human brain.4 Given the short half-life of 11C, limiting its availability, several 18F-labeled amyloid-binding PET radiopharmaceuticals have been developed, including 18F-florbetapir, 18F-flutemetamol and 18F-florbetaben, which have recently been approved by the US Food and Drug Administration (FDA) for clinical use.5–7 However, no single diagnostic test or imaging is considered sufficient. Amyloid imaging and cerebrospinal fluid CSF Aβ levels are considered markers of the neuropathologic process, whereas FDG-PET is considered a marker for neuronal damage, and their combined interpretation may aid a diagnosis of AD in the right clinical context.8 There has been a controversy regarding the overall and relative usefulness of these PET agents with respect to FDG-PET for diagnosing AD.9–11

18F-Florbetapir is a fluorine-labeled stilbene derivative. The recommended dose for 18F-florbetapir is 370 MBq (10 mCi). For routine clinical use, the scan is obtained as a 10-minute acquisition, starting 40 to 50 minutes after intravenous injection (Table 1). The effective radiation dose after a 10-mCi injection in an adult is 7.0 mSv.12 An excellent correlation between 18F-florbetapir and 11C-PiB uptake has been shown.13

Normal amyloid scans show a clear gray-white matter contrast, with more radioactivity concentration in white matter. In patients with AD, uptake is increased in the orbitofrontal cortex, anterior cingulate, precuneus, posterior cingulate, and lateral temporal cortex, consistent with autopsy findings in direct comparison studies (Fig. 1).2,14 According to some recommendations, the 18F-florbetapir scan is considered positive if either (1) 2 or more brain areas (each larger than a single cortical gyrus) show reduced or absent gray-white matter contrast, or (2) there are 1 or more areas in which gray matter uptake is intense and clearly exceeds the uptake in adjacent white matter. A potential pitfall of scan interpretation using these criteria is in cases with brain atrophy, in which the gray-white matter contrast may be lost because of atrophy rather than abnormal accumulation in the gray matter. Alternatively, the ratio of radiotracer concentration in the region of disease to either the whole brain or to pons has been proposed as a semiquantitative index of 18F-florbetapir uptake.15

On correlation with disease, a negative amyloid scan corresponded to a neuropathologic amyloid deposition rating (Consortium to Establish a Registry for Alzheimer’s Disease) of none to sparse, whereas a positive amyloid scan corresponded to a rating of moderate to frequent amyloid plaque deposition in the cortex.

Amyloid imaging can be useful in differentiating AD from frontotemporal dementia. Patients with frontotemporal dementia do not show significant amyloid deposition. However, abnormal amyloid deposition may be seen in 50% to 70% of patients with dementia with Lewy bodies (DLB) (Table 2).16 Negative 18F-florbetapir PET scans have been reported for some clinically diagnosed patients with AD, consistent with literature reports that 10% to 20% of clinically diagnosed patients with AD do not have amyloid disease at autopsy.17