Background: Alzheimer’s disease (AD) is the most common form of dementia. Neuroimaging
methods have widened the horizons for AD diagnosis and therapy. The goals of this work are the synthesis
of 2-(3-fluoropropyl)-6-methoxynaphthalene (5) and its [18F]-radiolabeled counterpart
([18F]Amylovis), the in silico and in vitro comparative evaluations of [18F]Amylovis and [11C]Pittsburg
compound B (PIB) and the in vivo preclinical evaluation of [18F]Amylovis in transgenic and wild mice.
Methods: Iron-catalysis cross coupling reaction, followed by fluorination and radiofluorination steps were
carried out to obtain 5 and 18F-Amylovis. Protein/Aß plaques binding, biodistribution, PET/CT Imaging
and immunohistochemical studies were conducted in healthy/transgenic mice.
Results: The synthesis of 5 was successful obtained. Comparative in silico studies predicting that 5
should have affinity to the Aβ-peptide, mainly through π-π interactions. According to a dynamic simulation
study the ligand-Aβ peptide complexes are stable in simulation-time (ΔG = -5.31 kcal/mol).
[18F]Amylovis was obtained with satisfactory yield, high radiochemical purity and specific activity. The
[18F]Amylovis log Poct/PBS value suggests its potential ability for crossing the blood brain barrier (BBB).
According to in vitro assays, [18F]Amylovis has an adequate stability in time. Higher affinity to Aβ
plaques were found for [18F]Amylovis (Kd 0.16 nmol/L) than PIB (Kd 8.86 nmol/L) in brain serial sections
of 3xTg-AD mice. Biodistribution in healthy mice showed that [18F]Amylovis crosses the BBB with
rapid uptake (7 %ID/g at 5 min) and good washout (0.11±0.03 %ID/g at 60 min). Comparative PET dynamic
studies of [18F]Amylovis in healthy and transgenic APPSwe/PS1dE9 mice, revealed a significant
high uptake in the mice model.
Conclusion: The in silico, in vitro and in vivo results justify that [18F]Amylovis should be studied as a
promissory PET imaging agent to detect the presence of Aβ senile plaques.