Preferred features of a fluorine-19 MRI probe for amyloid detection in the brain.
Fluorine-19 magnetic resonance imaging (19F MRI) could be a promising approach for imaging amyloid deposition in the brain. However, the required features of a 19F MRI probe for amyloid detection remain unclear. In the present study, we investigated a series of compounds as potent 19F probes that could prevent the reduction in MR signal when bound to amyloid plaques in the brain. Each compound consists of styrylbenzoxazole as a core structure linked by a different length of polyethylene glycol (PEG) chain to one of three types of fluorine-labeled group: a trifluoroethoxy group, a hexafluoroisopropoxy group, or a 3',5'-bis(trifluoromethyl)benzylamino group. Among these compounds, 6-(3',6',9',15',18',21'-heptaoxa-23',23',23'-trifluoro tricosanyloxy)-2-(4'-dimethylaminostyryl)benzoxazole [compound 3b (m = 6)], which has a trifluoroethoxy group with seven ethylene glycol groups in the PEG chain, showed significant 19F MR signals in the brains of AβPPswe/PS1dE9 double-transgenic mice, but not wild-type mice. This suggested that compound 3b (m = 6) could be a useful 19F MRI probe for amyloid detection. Furthermore, this study identified the most effective length of PEG chain between the fluorine-labeled group and the core structure to ensure a strong MR signal when the probe is bound to amyloid plaques.
Molecular Neuroscience Research Center, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Japan.
Daijiro
D
Yanagisawa
Molecular Neuroscience Research Center, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Japan.
Hiroyasu
H
Taguchi
Molecular Neuroscience Research Center, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Japan.
Nor Faeizah
NF
Ibrahim
Biomedical MR Science Center, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Japan.
Shigehiro
S
Morikawa
Biomedical MR Science Center, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Japan.
Akihiko
A
Shiino
Biomedical MR Science Center, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Japan.
Toshiro
T
Inubushi
Northeastern Industrial Research Center of Shiga Prefecture, Nagahama, Japan.
Koichi
K
Hirao
Northeastern Industrial Research Center of Shiga Prefecture, Nagahama, Japan.
Nobuaki
N
Shirai
Otsuka Pharmaceutical Co., Ltd, Kawauchi-cho, Japan.
Takayuki
T
Sogabe
Molecular Neuroscience Research Center, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Japan.
Ikuo
I
Tooyama
D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D004195:Disease Models, Animal; D005462:Fluorine Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D053764:Presenilin-1 / Q000235:genetics; D011877:Radionuclide Imaging; D013997:Time Factors; D014316:Tritium
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D005462:Fluorine Radioisotopes; C508853:PSEN1 protein, human; D053764:Presenilin-1; D014316:Tritium
Alzheimer's disease; amyloid deposition; amyloid imaging; fluorine-19 MRI; magnetic resonance imaging