Test-retest characteristic of [18F]MK-6240 quantitative outcomes in cognitively normal adults and subjects with Alzheimer's disease

J Cereb Blood Flow Metab. 2020 Nov;40(11):2179-2187. doi: 10.1177/0271678X19887781. Epub 2019 Nov 11.

Abstract

[18F]MK-6240 is a selective, high-affinity PET radiotracer for imaging neurofibrillary tangles (NFT) in Alzheimer's disease (AD). Herein, we report test-retest (T-RT) reproducibility of [18F]MK-6240 in AD and healthy volunteers (HV). Twelve subjects with AD and three cognitively normal HV were enrolled in the study and dynamically scanned for 150 min with [18F]MK-6240 under a T-RT protocol. Two radioactivity doses were investigated: 165 ± 3 MBq (n = 6) and 300 ± 40 MBq (n = 9). Serial arterial blood samples were taken for each scan to obtain metabolite-corrected input functions. Following intravenous administration of [18F]MK-6240, the tracer rapidly partitioned into the brain and its heterogenous distribution pattern was consistent with known NFT pathology in AD. In contrast, uptake in HV was low and uniform across the brain parenchyma. Across all subjects, average T-RT variabilities in NFT-rich regions were ∼21%, ∼14% and ∼6% for various quantitative metrics: total distribution volume (VT), binding potential (BPND), and standardized uptake ratio (SUVR90-120), respectively. No significant differences in SUVR T-RT variability were observed between the high and low injected radioactivity groups (5.6% and 6.1%, respectively). This work suggests [18F]MK-6240 has adequate SUVR T-RT characteristics supporting the use of this outcome in future studies.

Keywords: Alzheimer’s disease; PET; [18F]MK-6240; tau; test–retest.

MeSH terms

  • Adult
  • Alzheimer Disease / diagnosis*
  • Brain / diagnostic imaging*
  • Brain / physiology*
  • Cognition*
  • Female
  • Fluorodeoxyglucose F18*
  • Humans
  • Isoquinolines*
  • Male
  • Neurofibrillary Tangles / pathology*
  • Positron-Emission Tomography* / methods

Substances

  • Isoquinolines
  • MK-6240
  • Fluorodeoxyglucose F18