Quantitative PET required to avoid pitfalls of amyloid imaging over time

Variability in longitudinal standard uptake value ratios when imaging Alzheimer’s patients with C-11 PiB and other amyloid agents create inaccurate portraits of disease progression, warranting a fully quantitative PET protocol for long-term research, according to a study published online Aug. 12 in the Journal of Nuclear Medicine.

Bart N.M. van Berckel, MD, PhD, from the department of Nuclear Medicine and PET Research at VU University Medical Center in Amsterdam, The Netherlands, and colleagues completed an analysis of PET data acquisition to identify the best methodology for assessing longitudinal C-11 PiB binding patterns related to Alzheimer’s disease (AD).

“Previous studies using C-11 PiB have shown high diagnostic accuracy for the detection of AD,” wrote Berckel et al. “Longitudinal studies, however, have provided inconsistent findings with either no or modest changes in C-11 PiB binding over time in AD patients. Apart from other methodologic considerations, one possible explanation for these inconsistent results could be the method used to quantify specific C-11 PiB binding.”

A total of seven Alzheimer’s patients, 11 patients with mild cognitive impairment and another 11 healthy controls underwent dynamic 90-minute PET imaging at the beginning of the study and at approximately 30 months after initial amyloid imaging with C-11 PiB.

Quantitative PET was performed using three methods including standardized uptake volume ratios for intervals between 40 and 60 (SUVr 40-60) and between 60 and 90 (SUVr 60-90),  as well as reference parametric mapping and reference Logan values. Cerebellar gray matter was the reference region for all methods and researchers evaluated the percentage change between outset and follow-up to assess their effectiveness for longitudinal amyloid studies. Results showed that statistical data acquisition with reference parametric mapping showed less variability than standardized uptake volume methods, which tended to overestimate C-11 PiB binding.

“It is already known that, in AD patients, flow changes over time occur because of disease progression, and, consequently, it may be expected that this will result in more variability in SUVr over time,” wrote the authors. “Changes in [tracer delivery to the cortex relative to that of the cerebellum] seen in AD patients indicate that these flow changes are indeed present. Therefore, it is highly likely that changes in SUVr observed in the present series of AD patients do not reflect changes in specific C-11 PiB binding but are rather due to changes in perfusion during the course of the disease.”

Findings showed 10 percent overestimation of tracer binding for SUVr 40-60 and 13 percent for SUVr 60-90 with high variability between patients when compared to reference parametric mapping and, on average, reference Logan values were about 6 percent lower than reference parametric mapping.  

By follow up, C-11 PiB delivery decreased only in AD patients and simulations revealed that SUVr methods were vulnerable to changes in flow and strongly dependent on uptake period.  

“As such, these findings imply that any study [but particularly when using C-11 PiB or tracers with similar kinetic behavior] where variations in blood flow can be expected should not be analyzed using SUVr,” the researchers wrote. “Consequently, for accurate quantification of longitudinal amyloid imaging studies, dynamic scanning protocols and fully quantitative data analysis methods are essential. This is especially true for longitudinal studies with disease-modifying agents aiming to lower amyloid load in the brain.”