Quantification of [18F]florbetapir: A test-retest tracer kinetic modelling study

Abstract

Accumulation of amyloid beta can be visualized using [¹⁸F]florbetapir positron emission tomography. The aim of this study was to identify the optimal model for quantifying [¹⁸F]florbetapir uptake and to assess test-retest reliability of corresponding outcome measures. Eight Alzheimer's disease patients (age: 67 ± 6 years, Mini-Mental State Examination (MMSE): 23 ± 3) and eight controls (age: 63 ± 4 years, MMSE: 30 ± 0) were included. Ninety-minute dynamic positron emission tomography scans, together with arterial blood sampling, were acquired immediately following a bolus injection of 294 ± 32 MBq [¹⁸F]florbetapir. Several plasma input models and the simplified reference tissue model (SRTM) were evaluated. The Akaike information criterion was used to identify the preferred kinetic model. Compared to controls, Alzheimer's disease patients had lower MMSE scores and evidence for cortical Aβ pathology. A reversible two-tissue compartment model with fitted blood volume fraction (2T4k_V_B) was the preferred model for describing [¹⁸F]florbetapir kinetics. SRTM-derived non-displaceable binding potential (BP_ND) correlated well (r² = 0.83, slope = 0.86) with plasma input-derived distribution volume ratio. Test-retest reliability for plasma input-derived distribution volume ratio, SRTM-derived BP_ND and SUVr_(50-70) were r = 0.88, r = 0.91 and r = 0.86, respectively. In vivo kinetics of [¹⁸F]florbetapir could best be described by a reversible two-tissue compartmental model and [¹⁸F]florbetapir BP_ND can be reliably estimated using an SRTM.

Keywords: Alzheimer’s disease; Amyloid positron emission tomography; [18F]florbetapir; test–retest; tracer kinetic modelling.

Figure 1.

Parent [¹⁸F]florbetapir and polar metabolite fractions (mean ± SD) in arterial plasma at different time points.

Figure 2.

Comparison of SRTM-derived BP_ND against plasma input (Original IP)-derived DVR. Original IP is the input function obtained using original parent fractions. AD: Alzheimer’s disease; C: controls; DVR: distribution volume ratio; SRTM: simplified reference tissue model; BP_ND: non-displaceable binding potential; IP: input; LOI: line of identity.

Figure 3.

(a) Average whole brain grey matter SUVr values as function of time for each subject. Different symbols represent subjects (red lines are AD patients and blue lines are controls). (b) Comparison of SUVr obtained from data of different scan durations (40–50 min, 50–60 min and 50–70 min) against DVR, for all regions of interest included in the Hammers template. AD: Alzheimer’s disease; C: controls; DVR: distribution volume ratio; SUVr: standardized uptake value ratio.

Figure 4.

%TRT reliability of (a) V_T and (b) DVR observed in all Hammers template defined brain regions of both AD patients and controls, when using either of the three input functions. Original IP is the input function obtained using original parent fractions; POP IP is the input function obtained using population average parent fractions; Intra-pat IP is the input function obtained using intra subject average (test–retest) parent fractions. TRT: test–retest; DVR: distribution volume ratio.

Figure 5.

Impact of scan duration on kinetic parameter estimates: V_T (a, b and c), DVR (d, e and f), SRTM BP_ND (g, h and i). Reliability of estimated parameters decreased for shorter scan durations, similarly between test (red points) and retest (blue points) data. DVR: distribution volume ratio; LOI: line of identity.