Amyloid PET imaging in Alzheimer's disease: a comparison of three radiotracers

Abstract

Purpose: The increasing use of amyloid PET in Alzheimer's disease research and clinical trials has motivated efforts to standardize methodology. We compared retention of the (11)C radiotracer Pittsburgh Compound B (PiB) and that of two (18)F amyloid radiotracers (florbetapir and flutemetamol) using two study populations. We also examined the feasibility of converting between tracer-specific measures, using PiB as the common link between the two (18)F tracers.

Methods: One group of 40 subjects underwent PiB and flutemetamol imaging sessions and a separate group of 32 subjects underwent PiB and florbetapir imaging sessions. We compared cortical and white matter retention for each (18)F tracer relative to that of PiB, as well as retention in several reference regions and image analysis methods. Correlations between tracer pairs were used to convert tracer-specific threshold values for amyloid positivity between tracers.

Results: Cortical retention for each pair of tracers was strongly correlated regardless of reference region (PiB-flutemetamol, ρ = 0.84-0.99; PiB-florbetapir, ρ = 0.83-0.97) and analysis method (ρ = 0.90-0.99). Compared to PiB, flutemetamol had higher white matter retention, while florbetapir had lower cortical retention. Two previously established independent thresholds for amyloid positivity were highly consistent when values were converted between tracer pairs.

Conclusion: Despite differing white and grey matter retention characteristics, cortical retention for each (18)F tracer was highly correlated with that of PiB, enabling conversion of thresholds across tracer measurement scales with a high level of internal consistency. Standardization of analysis methods and measurement scales may facilitate the comparison of amyloid PET data obtained using different tracers.

Figure 1

Bar plots comparing retention for each tracer in subcortical white matter and the cortical composite region relative to brainstem/pons, cerebellar grey matter, and whole cerebellum are shown for (A) the flutemetamol-PiB group and (B) the florbetapir-PiB group. Asterisks represent significant differences for each pair of regional associations.

Figure 2

Associations between summary cortical composite retention ratios are plotted for (A) subjects who received flutemetamol and PiB scans and (B) subjects who received florbetapir and PiB scans. Three reference regions (left, brainstem/pons; middle, cerebellar grey matter; and right, whole cerebellum) were used. Linear regression equations and Spearman’s rho correlations are given for each association.

Figure 3

Example associations between the two image processing methods are shown (see complete list of associations across tracers and reference regions in Table 3). Linear regression equations and Spearman’s rho correlations are shown representing associations between the Freesurfer-based and adaptive template-based cortical composite values for A) flutemetamol and B) florbetapir, each with brainstem/pons and whole cerebellum normalization.

Figure 4

Two previously established thresholds for cortical amyloid positivity can be converted between radiotracers using PiB as the link between flutemetamol and florbetapir. For example (A), a PiB-based threshold of 1.47 was converted to florbetapir and flutemetamol units, each linear regression equation to convert 1.47 (PiB units, cerebellar grey matter normalization) to 1.13 (florbetapir units, whole cerebellum normalization) and to 1.20 (flutemetamol units, whole cerebellum normalization). In a second example (B), a florbetapir-based threshold of 1.11 (whole cerebellum normalized) was converted to PiB units (1.27, whole cerebellum normalization), and this new PIB threshold was in turn converted to flutemetamol units, resulting in a value value (1.20, whole cerebellum) that is almost identical to the flutemetamol threshold calculated from the first threshold (A, flutemetamol threshold 1.21).