Fluoro-pegylated (FPEG) Imaging Agents Targeting Aβ Aggregates

Abstract

A novel approach of producing positron emission tomography (PET) imaging agents through the formation of bioconjugates based on pegylation-fluorination strategy resulting in fluoro-pegylated (FPEG) molecules is reported. This approach offers a simple and easy method by which to incorporate 18

Preliminary evaluation of fluoro-pegylated benzyloxybenzenes for quantification of β-amyloid plaques by positron emission tomography

“…This result was consistent with that of previous report [11]. As the length of FPEG increased, a decline in binding ability was observed (K i : 5a < 5b < 5c, 5d < 5e < 5f), which differed from the structure-activity relationships of benzoheterocycle [15,16] and stilbene [17,18] derivatives. Among these FPEG derivatives, the N,N-dimethylated ligands 5a and 9a with a short FPEG side chain (n ¼ 1) exhibited the most potent binding affinity with K i values of 25.7 ± 2.6 and 21.0 ± 4.9 nM, respectively, which were in the same range as that of well-established IMPY (K i ¼ 32.2 ± 2.1 nM), PIB (K i ¼ 38.8 ± 2.6 nM) and AV-45 (K i ¼ 11.4 ± 1.1 nM) under identical assay conditions.…”

Quick Assembly of 1,4-Diphenyltriazoles as Probes Targeting β-Amyloid Aggregates in Alzheimer's Disease

“…18,42,43 The "hot" fluorination reaction can be readily accomplished by a nucleophilic substitution of a mesylated or tosylated terminal leaving group by an activated fluoride ion. When a fluoropegylated chain was added to one end of the phenyl group, it led to two active diphenyltriazoles, 13a and 13c.…”

Fluorinated Benzofuran Derivatives for PET Imaging of β-Amyloid Plaques in Alzheimer's Disease Brains

“…Uptake in the bone at 60 min was measurable (2.74% ID/g), suggesting little defluorination in vivo. 13,19,26 However, the free fluoride was not taken up by brain tissue, and so, interference with the imaging is expected to be relatively minor.…”