Amyloid Imaging

3.7.1 Radiopharmaceutical

Three PET tracers are approved for imaging amyloid aggregates by the EMA:

• [¹⁸F]florbetapir (Amyvid™);
• [¹⁸F]flutemetamol (Vizamyl™);
• [¹⁸F]florbetaben (NeuraCeq™).

3.7.2 Uptake mechanism/biology of the tracer

Amyloid PET tracers bind to β-sheets of amyloid aggregates as they occur in the brain cortex of subjects with AD or other neurodegenerative disorders.

3.7.3 Indications

In Europe, indications for amyloid PET imaging are geared to the appropriate use criteria (AUC) published by the US-based Society of Nuclear Medicine and Molecular Imaging (SNMMI) and Alzheimer Association (AA). These AUC emphasize that amyloid PET is currently most likely to be helpful when the patient has objectively confirmed cognitive impairment, when the cause of cognitive impairment remains uncertain after a comprehensive evaluation by a dementia expert and the differential diagnosis includes AD dementia, and when the knowledge of the presence or absence of Aβ pathology is expected to increase diagnostic certainty and/or alter patient management. Under these premises, the use of amyloid PET is considered appropriate in patients with any of the following conditions:

• Persistent or progressive unexplained mild cognitive impairment.
• The core clinical criteria for possible AD are satisfied, but there is an unclear clinical presentation-either an atypical clinical course or an etiologically mixed presentation.
• Patients with progressive dementia and atypically early age of onset (usually defined as 65 years or less in age).

3.7.4 Contraindications

• Amyloid PET imaging is absolutely contraindicated in case of pregnancy.
• Breast feeding should be interrupted for 12 hrs following the examination [3].

According to the SNMMI/AA AUCs, the use of amyloid PET is considered inappropriate for:

• Patients with core clinical criteria for probable AD with typical age of onset;
• Determination of dementia severity;
• Individuals with a positive family history of AD or have been shown to carry the     ε4 allele of apolipoprotein E;
• Patients with a cognitive complaint that is unconfirmed on clinical examination;
• In lieu of genotyping for suspected autosomal dominant mutation carriers;
• Asymptomatic individuals;
• Nonmedical use (e.g., legal, insurance coverage, or employment screening).

3.7.5 Clinical performances

The amyloid PET tracers have a high sensitivity/specificity (~94%/~97%) for detecting/excluding neuritic amyloid plaques. Preliminary data also point to a relevant clinical utility (change of diagnosis, increase of diagnostic confidence, change of management, cost-efficacy) of these tracers.

3.7.6 Activities to administer

The suggested activities to administer for adults range 370 MBq for [¹⁸F]florbetapir, 185 MBq for [¹⁸F]flutemetamol and 300 MBq for [¹⁸F]florbetaben.

No recommendations are given for paediatric nuclear medicine.

3.7.7 Dosimetry

The effective dose per administered activity is 19 µSv/MBq (generic model for brain receptor substances) [3].

The range of the effective doses for the suggested activities is: 3.5-7 mSv.

Caveat

“Effective Dose” is a protection quantity that provides a dose value related to the probability of health detriment to an adult reference person due to stochastic effects from exposure to low doses of ionizing radiation. It should not be used to quantify the radiation risk for a single individual associated with a particular nuclear medicine examination. It is used to characterize a certain examination in comparison to alternatives, but  it should be emphasized that if the actual risk to a certain patient population is to be assessed, it is mandatory to apply risk factors (per mSv) that are appropriate for the gender, the age distribution and the disease state of that population."

3.7.8 Interpretation criteria/major pitfalls

Amyloid PET examinations should be performed by, or under supervision of, a physician certified in nuclear medicine. Physicians who interpret amyloid PET should also complete appropriate training programs provided by the manufacturers of approved radiotracers. Amyloid PET images are assessed by standardized visual read, and the results are reported in a binary (amyloid-positive versus -negative) fashion. The specific criteria for amyloid PET image interpretation differ slightly among available tracers, and readers should be aware of the European Medicine Agency (EMA) recommendations specific to a given amyloid tracer. The reader is referred to the SNMMI Procedure Standard/EANM Practice Guideline for Amyloid PET Imaging of the Brain 1.0 [85].

Major pitfalls might relate to head movement or brain atrophy, both potentially simulating amyloid-positivity.

3.7.9 Patient preparation

For specific patient preparation, see the SNMMI Procedure Standard/EANM Practice Guideline for Amyloid PET Imaging of the Brain 1.0 [85].

3.7.10 Methods

For specific methods description, see the SNMMI Procedure Standard/EANM Practice Guideline for Amyloid PET Imaging of the Brain 1.0 [85].