Increased in vivo binding of [¹⁸F]FEMPA to the 18-kDa translocator protein in Alzheimer`s disease

Objectives [¹⁸F]FEMPA is a novel high-affinity radioligand for the 18-kDa translocator protein (TSPO), displaying suitable pharmacokinetic properties in pre-clinical studies. The aim of this study was to assess whether [¹⁸F]FEMPA could detect in vivo increased TSPO binding in Alzheimer`s disease (AD) patients.

Methods Ten AD patients (5M/5F, age 66.9±7.3 y, MMSE 25.5±2.5) and seven controls (3M/4F, age 63.7±7.2 y, MMSE 29.3±1.0) were studied using [¹⁸F]FEMPA at Turku (n=13) and at Karolinska Institutet (n=4). The in vitro binding affinity for TSPO was assessed using PBR28 in a competition assay with [³H]PK11195 in 7 controls and 8 AD patients. Cortical and subcortical regions-of-interest were examined. Quantification was performed using Logan graphical analysis. The outcome measure was the total distribution volume (V_T). Multivariate analysis was used to assess the effect of group or TSPO binding profile on V_T.

Results Five AD and 4 controls were high-affinity binders (HABs). Three AD and 3 controls were mixed-affinity binders. In the medial temporal cortex, a significant difference of V_T (p=0.044) was found if the TSPO binding profile was entered as covariate. If only HABs were included, significant differences of V_T (p<0.05, Figure) were found in the medial and lateral temporal cortex, caudate, putamen, thalamus, posterior cingulate, and cerebellum.

Conclusions [¹⁸F]FEMPA seems to be a suitable radioligand to detect increased TSPO binding in AD if the binding status is taken into account.

Research Support The study was supported by Bayer Healthcare AG. The compound is now part of the portfolio of the Piramal Imaging GmbH, Berlin, Germany.