Dual-tracer PET/CT Imaging using 18F-AV-45 and 18F-AV-1451 for the Diagnosis of Alzheimer's Disease

Summary

This protocol describes the standardized procedure for dual-tracer PET/CT imaging using ¹⁸F-AV-45 and ¹⁸F-AV-1451 in patients with suspected Alzheimer’s disease (AD). It includes patient preparation, tracer administration, image acquisition, and interpretation criteria, as well as representative imaging features of amyloid and tau pathology.

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by an insidious onset and gradual deterioration. Clinically, it manifests as cognitive decline and behavioral changes rather than only as generalized dementia. Currently, the diagnostic accuracy of AD remains limited due to the nonspecific clinical manifestations and the low specificity of conventional examinations such as neuropsychological assessments, electroencephalography (EEG), computed tomography (CT), and magnetic resonance imaging (MRI). Positron emission tomography/computed tomography (PET/CT) provides detailed structural and functional information along with specific molecular distributions, making it increasingly valuable for the diagnosis and research of AD. We performed PET/CT scans using the radiotracers ¹⁸F-AV-45 (florbetapir) and ¹⁸F-AV-1451 (flortaucipir). The key distinction between these tracers lies in their molecular targets: ¹⁸F-AV-45 binds to β-amyloid (Aβ), whereas ¹⁸F-AV-1451 specifically targets tau protein. This study elaborates on the protocol for the combined use of both tracers in AD diagnosis, encompassing patient preparation procedures, image acquisition techniques, interpretation standards, and the clinical significance of their joint application. This dual-tracer protocol provides a sensitive, comprehensive, and non-invasive method for detecting both amyloid and tau pathology, enhancing early diagnosis, disease staging, and research on disease progression.

Introduction

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by a slow onset and progressive deterioration of cognitive function. Clinically, it presents with subjective cognitive decline (SCD), mild cognitive impairment (MCI), memory deficits, executive dysfunction, aphasia, and behavioral changes¹. The hallmark pathological features of AD include the deposition of β-amyloid (Aβ) plaques and the formation of neurofibrillary tangles composed of hyperphosphorylated tau protein. These pathological markers are key diagnostic criteria for AD and serve as primary molecular targets for imaging and biomarker studies.....

Protocol

This study was approved by the Medical Ethics Committee of The First Affiliated Hospital, Zhejiang University School of Medicine (Ref. IIT20210007C-R2). All participants provided written informed consent before participation, and the study was conducted in accordance with the Declaration of Helsinki. The reagents and the equipment used are listed in the Table of Materials.

1. Expert qualifications

1. Ensure that the evaluating physician has specialized training in neurology or psychiatry, and that at least 50% of their clinical practice involves the assessment and management of patients with cogn....

Results

Typical image features of amyloid PET
Typical amyloid PET–negative imaging features include the “ridge sign” (the gradient phenomenon formed by the uptake difference between gray and white matter, most evident in the temporo-occipital lobes on axial images), the “double convex lens sign” (a spindle-shaped phenomenon caused by the separation of the high-uptake white matter in the centrum semiovale by adjacent low-uptake gray matter, observed at the level of the centrum semiovale on axial images), and .......

Discussion

Alzheimer’s disease (AD) represents the most common cause of dementia worldwide. Conventional diagnostic approaches, including cognitive testing, CT, and MRI, often lack specificity, particularly during the early stages of disease progression. Dual-tracer PET/CT imaging provides a molecular imaging strategy that allows for the in vivo visualization of the key pathological proteins of AD—β-amyloid and tau—offering improved accuracy in disease characterization and staging.

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Audiovisual isolation (earplugs, eye mask)	3M Company	1100 Earplugs; generic eye mask	Reduce sensory input during the rest period.
Foam pads and restraining straps	Qfix	RT-4542	Minimize the motion of head and limbs.
Headrest	CIVCO Radiotherapy	MTAP100	Head immobilization during the scan.
Image analysis software	Beijing MedEx	MEMRS-NM-C	Semi-quantitative analysis and VOI-based assessments.
Image reconstruction workstation	Siemens Healthineers	syngo.via	PET/CT reconstruction and image fusion.
IV extension set / 3-way stopcock	BD	20045	Secure the injection line and perform a saline flush.
Peripheral IV catheter (20–22G)	BD	Insyte Autoguard 20G	Establish peripheral venous access.
PET/CT scanner	Siemens Healthineers, Germany	Biograph Vision	Acquisition of PET and CT images.
Sterile syringes (5 mL / 10 mL)	BD	Ref. 309604	Radiotracer injection.
Thermometer/hygrometer	Testo	608-H1	Maintain room temp (~26°C) during uptake.