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brain scan pet imaging for alzheimers

Neurologic PET

Exploring neurological indications in PET and PET/CT

PET brain imaging provides a functional assessment and observes brain activity and metabolic processes. PET effectively detects beta-amyloid plaque, tau deposits, glucose or amino acid metabolism, and dopamine receptors in the brain.1 PET brain imaging can often detect changes in brain function and metabolism before other conventional imaging modalities like MRI or CT scans. Early detection can be vital for diagnosing neurological conditions sooner when interventions may be more effective. Alzheimer's Disease, Parkinson's Disease, and Epilepsy are common indications for PET neuroimaging.

Alzheimer's Disease

Neurodegenerative disorders are increasingly becoming more prevalent as population ages and life expectancies increase. Dementia is a common term to describe symptoms impacting a person's cognitive abilities. The most common type of dementia is Alzheimer's disease (AD), accounting for 60% -70% of all dementia diagnoses.2 As of 2021, AD is the sixth leading cause of death in the United States, and approximately 6.2 million Americans live with the disease.3 


AD develops slowly and worsens over time, and the rate in which a patient declines may vary.6 Patients diagnosed with AD live between three to eleven years, with some living up to 20 years post diagnosis.7 Statistics reveal that patients who live to 70-80 years of age will spend an average of 40% of that time in the severe stage.7 Therefore, the age at which a person is diagnosed often has the most significant impact on determining life expectancy.8 While current AD medications don't cure the disease, they may improve quality of life and prolong independence.

Clinicians can often determine whether a patient has dementia, but identifying the cause can be difficult. There is not one specific test to diagnose Alzheimer’s disease (AD). Instead, clinicians use a series of tools and tests, including medical and family history, cognitive and neurological tests to assess thinking and physical function, and blood tests or brain imaging (CT, PET, or structural MRI).4,5

An early diagnosis can offer the patient and their family valuable time to make decisions regarding medical care and needs.

The value of knowing

Participate in planning of care for their loved one

For loved ones

  • Participate in planning of care for their loved one
  • Address safety issues and concerns

β-amyloid imaging

Patients with symptoms of cognitive impairment are often misdiagnosed with Alzheimer's disease (AD). The only definitive method to diagnose AD is a neuropathological examination, usually performed during an autopsy.9 Up to one in five patients clinically diagnosed with probable Alzheimer's disease during life do not have AD pathology upon autopsy.9 With no single test available to offer a definitive diagnosis, the path to obtaining a diagnosis can be a cumbersome and a prolonged evaluation process which often includes a neuropsychological assessment, routine blood tests, and conventional imaging like CT or MRI.4,5

One of the significant advances in AD research is the development of PET biomarkers targeted specifically for detecting beta-amyloid plaques and tau protein tangles.10 The USFDA approved amyloid-β PET in 2012, and in 2013 the Centers for Medicare and Medicaid (CMS) issued a National Coverage Determination (NCD) allowing conditional coverage with a 'coverage with evidence development' (CED) in clinical studies that meet specific criteria.

On October 13, 2023, CMS retired the NCD and eliminated previous CED requirements, including removing the once-in-a-lifetime requirement for beta-amyloid PET imaging. This change will now allow Medicare Administrative Contractors (MACs) to determine Medicare coverage for patients. SNMMI and other leading industry experts have advocated for this change and continue to urge CMS to eliminate other outdated PET NCDs that restrict coverage.11

"SNMMI applauds CMS for recognizing the pivotal role of amyloid PET scans in effectively managing Alzheimer's and other dementias"11
Society of Nuclear Medicine and Molecular Imaging
October 13, 2023
Healthy brain - Beta-amyloid protein fragments are broken down and removed from the brain

Healthy brain 

β-amyloid protein fragments are broken down and removed from the brain

Alzheimer's brain - Beta-amyloid protein fragments accumulate to form hard, insoluble plaques between neurons

Alzheimer's disease brain 

β-amyloid protein fragments accumulate to form hard, insoluble plaques between neurons


Data has shown that beta-amyloid plaques can begin to accumulate 20-25 years before the clinical onset of the disease, suggesting that β-amyloid is involved in the pathophysiology of AD.7 The use of β-amyloid PET imaging may help enable the quantification of β-amyloid plaque burden in the brain cortices as well in the blood vessels supplying the brain. Because β-amyloid plaques are found in all patients with AD, the use of β-amyloid PET imaging may play an important role in diagnosis.12 A positive β-amyloid PET scan is not a definitive diagnosis for Alzheimer's disease but rather a diagnostic tool to determine the presence of β-amyloid plaques in the brain to help increase the clinical certainty of AD diagnosis.12

β-amyloid plaques 

Amyloid neg and pos with MRI


Data courtesy of University TN Medical Center, Knoxville, TN, USA

β-amyloid plaques are seen in other neurologic conditions and older people with normal cognition; therefore the confirmation of β-amyloid plaques does not definitively lead to AD diagnosis.

New IDEAS study 

Even with over a decade of PET amyloid imaging studies, there has been little-to-no impact on patient outcomes. The first IDEAS study was the largest CMS-approved study and provided the most robust Phase IV data supporting the clinical utility of β-amyloid PET imaging.13 However, gaps were identified in the first study, which required further investigation to confirm appropriate use. 

The objectives of the new IDEAS study include:13

  • Determining whether β-amyloid imaging assists clinicians in providing a more accurate diagnosis and improved treatment decisions
  • Aiming to be the most racially and ethnically diverse study ever launched
  • Improving health equity by offering Alzheimer's disease research results that are relevant across diverse populations
beta-amyloid delivery radius
PETNET Pharmacies distributing beta-amyloid as of January 1, 2024

Access to beta-amyloid

PETNET produces and delivers beta-amyloid and tau PET imaging biomarkers for Alzheimer's disease and other neurological PET studies across the United States. The SNMMI offers a map locator to find hospitals or imaging centers offering beta-amyloid PET. SNMMI Brain imaging portal

Theranostics for neurodegenerative diseases 

In April of 2022, CMS announced that all USFDA-approved anti-amyloid immunotherapies would be subject to coverage with evidence development (CED) for patients with a clinical diagnosis of mild cognitive impairment (MCI) due to AD or mild AD dementia, both with confirmed presence of β-amyloid buildup consistent with AD.14 The October 13, 2023 decision by CMS to eliminate the CED requirements and allow MACs to determine appropriate coverage will lead to improved accessibility to beta-amyloid imaging and evaluate the use of new therapies as they become available.

Research and drug development are dynamic, with new drugs and therapies often emerging; as of January 2024, there are currently two FDA-approved drugs to treat patients with early-stage Alzheimer's disease.

Aducanumab

Aducanumab was the first FDA-approved therapy to treat early-stage Alzheimer's Disease. A beta-amyloid targeting therapy designed to reduce insoluble β-amyloid plaque was granted accelerated approval in June 2021 based on clinical trial results reducing beta-amyloid plaques by 59% to 71% over 18 months.15

Research and drug development are dynamic, with new drugs and therapies often emerging; as of January 2024, there are currently two FDA-approved drugs to treat patients with early-stage Alzheimer's disease.

Lecanemab

Lecanemab is an FDA-approved treatment to target amyloid proteins and reduce existing amyloid brain plaque. The traditional FDA-approval was granted based on data from the Clarity AD clinical trial, where the drug met the primary endpoint and all key secondary endpoints, confirming the clinical benefit of this targeted treatment.16

Parkinsonian syndromes

Parkinsonian syndromes is an umbrella term used to describe a group of neurological disorders sharing similar motor and non-motor symptoms closely related to Parkinson’s disease (PD). Some of the common parkinsonian syndromes include dementia with Lewy Bodies (DLB), Multiple System Atrophy (MSA), and vascular parkinsonism. These syndromes differ in their underlying causes; therefore, distinguishing between PD and other Parkinsonian syndromes is helpful because the underlying causes and treatment paths may vary significantly.17

PD is the most common cause of the syndrome and is a neurodegenerative disease often affecting the dopamine-producing neurons in the substantia nigra.17 There are more than 10 million global cases of PD, and the second most common neurodegenerative disease after AD.18 PD is referred to as a movement disorder due to the symptoms associated with the disease, including tremors, slowness, stiffness, and walking and balance issues. PD is a chronic and progressive condition leading to the gradual loss of dopamine-producing neurons, which, in turn, exacerbates over time, leading to the advancement of symptoms.18

In January 2020, the FDA approved Fluorodopa F-18 (F-Dopa) for visualizing dopaminergic neurons to evaluate suspected Parkinsonian syndromes. 
F-Dopa helps quantify the density of presynaptic nigrostriatal axons and assesses the activity of nigrostriatal aromatic amino acid decarboxylase (AADC) protein, an enzyme responsible for converting 18F-Dopa into 18F-dopamine, and indirectly estimates the dopaminergic storage pool.18

Refractory seizures



Types of epilepsy 

18F FDG PET/CT imaging is indicated for assessing patients with refractory epilepsy for pre-surgical evaluation.19 Epilepsy is a neurological disorder characterized by epileptic seizures caused by excessive neuronal activity in the brain. This neurological disorder affects approximately 65 million of the world’s population, with approximately 20%-40% of those diagnosed with refractory epilepsy.20 There are four main types of epilepsy:

Focal

The most common form of epilepsies often affects one brain area and can move to other places. This type can involve temporal, frontal, parietal, and occipital lobes, with the temporal lobe being most common. A seizure may be motor (physical activity) or non-motor (no physical movement).21,22

Generalized

Affects both the left and right sides of the brain and usually starts during childhood. A seizure may be motor (physical activity) or non- -motor (no physical movement).21,22

Focal and generalized

Involves both focal and generalized activity and results in having both focal and generalized seizures.21,22

Unknown

Unable to determine where the seizures originate.20,19

Fludeoxyglucose F 18 Injection (18F FDG)

Sharp cortical and striatal definition in pediatric patient with epilepsy

Coronal18F FDG Brain image

Coronal

Interictal Fludeoxyglucose F 18 (18F FDG) PET in a patient with pediatric epilepsy shows sharp definition of cortical sulci and gyri and caudate and putaminal margins
Sagittal 18F FDG Brain image

Sagittal

Small structures like superior colliculi and cerebellar peduncles sharply visualized due to high resolution 

Transverse 18F FDG brain image

Axial

No clear foci of interictal hypometabolism suggestive of epileptic foci delineated 

Data courtesy of Osaka City University, Japan


Identifying the ictal onset zone may provide improved management and surgical outcomes. Non-invasive techniques like EEG monitoring, magnetic resonance imaging (MRI), single photon emission tomography/computed tomography (SPECT/CT), and 18F FDG PET may be helpful in the localization of the seizure focus.20 

18F FDG measures glucose metabolism related to the synaptic and neuronal activity of the brain tissue.23 Most often, 18F FDG PET imaging is performed during the interictal phase as the ictal phase is unpredictable and makes imaging difficult due to the necessary resources required for the exam. Postictal imaging can be challenging to interpret, and uptake can vary depending on the timing of the 18F FDG injection.20 The uptake pattern with interictal 18F FDG PET may be affected by recent or ongoing seizure activity; thus, the use of electroencephalography (EEG) recording before and during the scan will assist in identifying when a seizure may be occurring.20   

Many studies have shown that 18F FDG PET may help predict surgical outcomes for patients with refractory epilepsy. In addition, 18F FDG has shown superior sensitivity for those with an equivocal MRI and EEG in determining the pre-surgical localization of epileptogenic foci with those with medically refractory partial epilepsy.20

18F  FDG PET imaging is CMS-approved in the US for pre-surgical evaluation for the purpose of localization of a focus of refractory seizure activity.24 


Reimbursement

Read more about reimbursement for neurological PET imaging

Important safety information

Fludeoxyglucose F 18 

Indications & usage

Fludeoxyglucose F 18 Injection (18F FDG) is indicated for positron emission tomography (PET) imaging in the following settings:

  • Oncology: For assessment of abnormal glucose metabolism to assist in the evaluation of malignancy in patients with known or suspected abnormalities found by other testing modalities, or in patients with an existing diagnosis of cancer.
  • Cardiology: For the identification of left ventricular myocardium with residual glucose metabolism and reversible loss of systolic function in patients with coronary artery disease and left ventricular dysfunction, when used together with myocardial perfusion imaging.
  • Neurology: For the identification of regions of abnormal glucose metabolism associated with foci of epileptic seizures.

Important safety information

  • Radiation Risk: Radiation-emitting products, including Fludeoxyglucose F18 Injection, may increase the risk for cancer, especially in pediatric patients. Use the smallest dose necessary for imaging and ensure safe handling to protect the patient and health care worker.
  • Blood Glucose Abnormalities: In the oncology and neurology setting, suboptimal imaging may occur in patients with inadequately regulated blood glucose levels. In these patients, consider medical therapy and laboratory testing to ensure at least two days of normoglycemia prior to Fludeoxyglucose F 18 Injection administration.
  • Adverse Reactions: Hypersensitivity reactions with pruritus, edema, and rash have been reported. Have emergency resuscitation equipment and personnel immediately available.

Dosage forms and strengths

Multiple-dose 30 mL and 50 mL glass vial containing 0.74 to 7.40 GBq/mL (20 to 200 mCi/mL) Fludeoxyglucose F 18 Injection and 4.5 mg of sodium chloride with 0.1 to 0.5% w/w ethanol as a stabilizer (approximately 15 to 50 mL volume) for intravenous administration.

Fludeoxyglucose F 18 Injection is manufactured and distributed by:
PETNET Solutions, Inc.
810 Innovation Drive
Knoxville, TN 39732

These highlights do not include all the information needed to use Fludeoxyglucose F 18 Injection safely and effectively. 

All rights reserved. All product/company names mentioned herein are the trademarks of their respective owners

1
Nuclear medicine neuro pet assessment, protocols, and interpretation. (n.d.). https://www.ncbi.nlm.nih.gov/books/NBK570591/ Nuclear medicine neuro pet assessment, protocols, and interpretation. (n.d.). https://www.ncbi.nlm.nih.gov/books/NBK570591/ 
2

Lattanzi S, Brigo F, Vernieri F, Silvestrini M. Visit-to-visit variability in blood pressure and Alzheimer's disease. J Clin Hypertens (Greenwich). 2018 May;20(5):918-924. doi: 10.1111/jch.13290. Epub 2018 Apr 25. PMID: 29693801; PMCID: PMC8031352.

3

Alzheimer’s Association, 2021 Alzheimer’s Disease Facts and Figures, Alzheimer’s Dement 2021; 17(3)

4

Mayo Clinic Staff. “Alzheimer's Stages: How the Disease Progresses.” Mayo Clinic, Mayo Foundation for Medical Education and Research, 29 Apr. 2021, https://www.mayoclinic.org/diseases-conditions/alzheimers-disease/in-depth/alzheimers-stages/art-20048448. 

5

Mayo Clinic Staff. “Learn How Alzheimer's Is Diagnosed.” Mayo Clinic, Mayo Foundation for Medical Education and Research, 7 May 2022, https://www.mayoclinic.org/diseases-conditions/alzheimers-disease/in-depth/alzheimers/art-20048075. 

6

Bateman, Randall J., et al. "Clinical and biomarker changes in dominantly inherited Alzheimer's disease." N Engl J Med 367 (2012): 795-804. 

7

Alzheimer’s Association. (2021). Alzheimer’s disease facts and figures. [Ebook]. Chicago. Retrieved from https://alz.org/media/Documents/alzheimers-facts-and-figures-2021.pdf 

8

“Alzheimer's Disease Fact Sheet.” National Institute on Aging, U.S. Department of Health and Human Services, https://www.nia.nih.gov/health/alzheimers-disease-fact-sheet. 

9

Lattanzi S, Brigo F, Vernieri F, Silvestrini M. Visit-to-visit variability in blood pressure and Alzheimer's disease. J Clin Hypertens (Greenwich). 2018 May;20(5):918-924. doi: 10.1111/jch.13290. Epub 2018 Apr 25. PMID: 29693801; PMCID: PMC8031352. 

10

Chen B, Marquez-Nostra B, Belitzky E, et al. PET Imaging in Animal Models of Alzheimer's Disease. Front Neurosci. 2022;16:872509. Published 2022 May 24. doi:10.3389/fnins.2022.872509 

11
SNMMI. (n.d.). CMS removes NCD for beta amyloid pet. https://www.snmmi.org/NewsPublications/NewsDetail.aspx?ItemNumber=45354 
12

FOR HEALTHCARE PROFESSIONALS Frequently asked questions about beta-amyloid imaging. (2021) https://www.alz.org/media/documents/health-care-pros-faqs-beta-amyloid-imaging.pdf 

13

“About Us New IDEAS Study.” About Us, https://www.ideas-study.org/About-Us#:~:text=The%20New%20IDEAS%20study%20will%20also%20have%20two%20additional%20objectives,have%20consented%20to%20blood%20collection. 

14

“Monoclonal Antibodies Directed against Amyloid for the Treatment of Alzheimer's Disease.” CMS.gov Centers for Medicare & Medicaid Services, https://www.cms.gov/medicare-coverage-database/view/ncacal-decision-memo.aspx?proposed=Y&NCAId=305.  

15
Aduhelm® (aducanumab-avwa): Official patient site. ADUHELM® (aducanumab-avwa) | Official Patient Site. (n.d.). https://www.aduhelm.com/ 
16
Learn about LEQEMBI® (lecanemab-irmb). Leqembi. (n.d.). https://www.leqembi.com/about-leqembi 
17
Rebecca Gilbert, M. (2023, July 13). The FDA approves F-DOPA pet imaging to aid in early diagnosis of parkinson’s disease. American Parkinson Disease Association. https://www.apdaparkinson.org/article/the-fda-approves-f-dopa-pet-imaging-to-aid-in-early-diagnosis-of-parkinsons-disease/ 
18
Emsen, B., Villafane, G., David, J.-P., Evangelista, E., Chalaye, J., Lerman, L., Authier, F.-J., Gracies, J.-M., & Itti, E. (2020, November 6). Clinical impact of dual-tracer FDOPA and FDG PET/CT for the evaluation of patients with Parkinsonian syndromes. Medicine. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7647518/ 
19

 Kumar A, Chugani HT. The role of radionuclide imaging in epilepsy, Part 1: Sporadic temporal and extratemporal lobe epilepsy. J Nucl Med. 2013;54(10):1775-1781. doi:10.2967/jnumed.112.114397 

20

Hodolic M, Topakian R, Pichler R. (18)F-fluorodeoxyglucose and (18)F-flumazenil positron emission tomography in patients with refractory epilepsy. Radiol Oncol. 2016;50(3):247-253. Published 2016 Jul 19. doi:10.1515/raon-2016-0032 

21

“4 Types of Epilepsy, Their Symptoms, and Treatments.” Medical News Today, MediLexicon International, https://www.medicalnewstoday.com/articles/types-of-epilepsy#contacting-a-doctor. 

Sarikaya I. PET studies in epilepsy. Am J Nucl Med Mol Imaging. 2015;5(5):416-430. Published 2015 Oct 12 

22

Fisher, Dr. Robert  S, et al. “Operational Claissification of Seizure Types by the International League Against Epilepsy’ Position Paper of the ILAE Commission for Classification and Terminology.” Https://Onlinelibrary.wiley.com/Doi/Epdf/10.1111/Epi.13670, Wiley Online Library, 8 Mar. 2017, https://onlinelibrary.wiley.com/doi/epdf/10.1111/epi.13670. 

23

Stanescu, Luana, et al. “FDG Pet of the Brain in Pediatric Patients: Imaging Spectrum with MR Imaging Correlation.” RadioGraphics, 30 Aug. 2013, https://pubs.rsna.org/doi/10.1148/rg.335125152. 

24

CMS.GOV. “FDG Pet for Refractory Seizures.” CMS.gov Centers for Medicare & Medicaid Services, https://www.cms.gov/medicare-coverage-database/view/ncd.aspx?NCDId=294&NCDver=1. 

25  
Mosconi, L., & McHugh, P. F. (2011, June). FDG- and amyloid-PET in Alzheimer’s disease: Is the whole greater than the sum of the parts? The quarterly journal of nuclear medicine and molecular imaging: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of... https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3290913/
26 
Duan, J., Liu, Y., Wu, H., Wang, J., Chen, L., & Chen, C. L. P. (2023, February 13). Broad learning for early diagnosis of alzheimer’s disease using FDG-Pet of the brain. Frontiers. https://www.frontiersin.org/articles/10.3389/fnins.2023.1137567/full
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