What type of beta amyloid Positron Emission Tomography (PET) scan is needed for Leqembi (lecanemab) treatment?

Beta Amyloid PET Scan Types for Leqembi (Lecanemab) Treatment

For Leqembi (lecanemab) treatment, any FDA-approved fluorine-18 (F-18) labeled amyloid PET tracer can be used, including florbetapir, flutemetamol, or florbetaben, as these have demonstrated high correlation with amyloid pathology and are widely available for clinical use. 1

Approved Amyloid PET Tracers

The FDA drug label for Leqembi specifically mentions that amyloid PET imaging is used to evaluate the effect of treatment on amyloid beta plaque levels in the brain 1. Several F-18 labeled tracers are available and appropriate:

• Florbetapir (Amyvid) - High sensitivity and specificity for detecting brain β-amyloid
• Flutemetamol (Vizamyl) - 100% concordance with PiB in visual scan categorization
• Florbetaben (Neuraceq) - High accuracy in detecting β-amyloid with good inter-reader agreement

These F-18 labeled tracers are preferred over carbon-11 Pittsburgh Compound B (PiB) for clinical use because:

• They have a longer half-life (110 minutes vs. 20 minutes for C-11)
• They can be produced at central cyclotron sites and delivered to clinical facilities
• They don't require an on-site cyclotron, making them more widely accessible 2

Clinical Correlation with PiB

All three F-18 tracers have been validated against the research standard C-11 PiB:

Tracer	Correlation with PiB	Visual Concordance
Florbetapir	r=0.78-0.95	97% agreement
Flutemetamol	r=0.905	100% concordance
Florbetaben	r=0.97	100% concordance

2

Interpretation and Clinical Use

The Leqembi FDA label states that PET imaging is quantified using:

• Standard uptake value ratio (SUVR)
• Centiloid scale to estimate amyloid beta plaque levels in brain areas affected by Alzheimer's disease 1

After 79 weeks of Leqembi treatment, 67% of patients had amyloid levels less than 30 Centiloids as measured by PET, which is considered a significant reduction 1.

Important Considerations

1. Qualitative vs. Quantitative Assessment:

   • Visual (qualitative) assessment by trained nuclear medicine specialists or radiologists
   • Quantitative assessment using standardized protocols for SUVR and Centiloid measurements

2. Timing of Scans:

   • Baseline scan before treatment initiation
   • Follow-up scans to monitor treatment response (typically at 12-18 months)

3. ApoE ε4 Status:

   • The FDA label recommends ApoE ε4 testing prior to treatment due to increased risk of ARIA (Amyloid-Related Imaging Abnormalities) in homozygotes 1
   • This genetic testing should be performed before initiating Leqembi

Common Pitfalls to Avoid

1. Misinterpreting Amyloid Positivity: A positive amyloid scan alone is not sufficient for AD diagnosis; clinical correlation is essential

2. Using Carbon-11 PiB: While it's the historical research standard, its short half-life makes it impractical for routine clinical use 2

3. Inadequate Training: Interpretation requires specific training in amyloid PET imaging

4. Failing to Consider Contraindications: Patients with significant cerebrovascular disease may have increased risk of ARIA with Leqembi treatment

In summary, any FDA-approved F-18 amyloid PET tracer (florbetapir, flutemetamol, or florbetaben) is appropriate for use with Leqembi therapy, with selection typically based on local availability and institutional experience.