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With the assistance of molecular docking and 3D-QSAR models established previously, structurally identical  18 F- and  125 I-labeled benzyloxybenzene derivatives were designed to achieve the early detection of A β  plaques by PET/SPECT imaging. In competition binding assay, ligands 7a and 12a displayed high binding affinities to A β  42  aggregates with  K  i  values of 19.5 nM and 23.9 nM, respectively. Specific plaque labeling was observed on the  in vitro  autoradiography of brain sections from AD patients and Tg mice. In biodistribution, [ 125 I]7a, [ 18 F]7a, [ 125 I]12a and [ 18 F]12a all exhibited high initial brain uptakes (>5% ID/g at 2 min). [ 125 I]7a and [ 125 I]12a cleared fast from the normal brain regions, while corresponding [ 18 F]7a and [ 18 F]12a showed slow washout rates. Dynamic microPET/CT and microSPECT/CT imaging data in normal ICR mice were in accordance with  in vivo  biodistribution results.  In vivo  metabolism results indicated that the different clearance profiles between the structurally identical  18 F- and  125 I-labeled tracers could be attributed to different biochemical characteristics of the radiometabolites. Radioiodinated benzyloxybenzene derivatives exhibited good  in vivo  biostability in brain. Ex vivo autoradiography further confirmed the strong  in vivo  A β  labeling ability of [ 125 I]7a. These new fluorinated and iodinated benzyloxybenzenes can develop into PET/SPECT dual imaging agents targeting A β  plaques.

scientific reports

Preliminary Characterization and In Vivo Studies of Structurally Identical 18F- and 125I-Labeled Benzyloxybenzenes for PET/SPECT Imaging of β-Amyloid Plaques