Comparison of the novel α4β2 nicotinic acetylcholine receptor PET radioligands (-)-Flubatine and (+)-Flubatine in Healthy Controls

Ziel/Aim:

Considering the urgent need of more suitable PET radioligands for imaging of nicotinic acetylcholine receptors (nAChR) of the α4β2 subtype we recently developed the second generation radiotracers (-)-F18-Flubatine and (+)-F18-Flubatine and investigated them for the first time in humans. Both showed favorable imaging characteristics. Aim of this study was to compare (-)-F18-Flubatine and (+)-F18-Flubatine in healthy controls focusing on their kinetic characteristics and assess potential fields of application.

Methodik/Methods:

For the current evaluation ten age and gender matched participants of the first in-human studies of (-)-F18-Flubatine and (+)-F18-Flubatine were selected from each study cohort. Kinetic parameters (1TCM) of 16 regions obtained from 0 – 90 min scans were compared.

Ergebnisse/Results:

We found similar K₁ values for both radioligands, except for cerebellar cortex and pons/midbrain where (-)-F18-Flubatine showed significantly higher K₁ values. In the majority of the investigated regions k₂ values were significantly higher for (-)-F18-Flubatine compared to (+)-F18-Flubatine. In cortical regions the specific binding (V/f_p) of both radioligands did not differ, whereas in subcortical regions (+)-F18-Flubatine showed a significantly higher binding than (-)-F18-Flubatine in thalamus, midbrain/pons and hypothalamus.

Schlussfolgerungen/Conclusions:

(-)-F18-Flubatine has a low level of metabolization, whilst (+)-F18-Flubatine shows virtually no metabolization. With regard to its faster kinetics the less toxic (-)-F18-Flubatine seems to be well suited for assessment of cortical and subcortical regions; preferably for inter-group comparisons, because in this situation a metabolite correction can presumably be neglected. (+)-F18-Flubatine does not require any metabolite correction and should therefore be particularly suitable to estimate kinetic parameters as accurate as possible, due to its significantly higher binding in regions with high α4β2 density it seems particularly suitable for imaging of α4β2 nAChRs in these regions.