Development and evaluation of [18F]Flotaza for Aβ plaque imaging in postmortem human Alzheimer’s disease brain

[124I]IBETA: A New Aβ Plaque Positron Emission Tomography Imaging Agent for Alzheimer’s Disease

“…In our in vitro studies using 5 × FAD mouse brains, the bromo analog of I-BETA (Br-BETA) and Flotaza—an unlabeled fluorine analog of a new PET radiotracer for imaging Aβ plaques ([ 18 F]Flotaza [ 15 ])—displaced >85% of [ 125 I]IBETA binding, suggesting a good correspondence in the binding sites of these two Aβ ligands. Since the binding of [ 125 I]IBETA was almost abolished completely in the presence of its bromo analog, a radiobrominated analog of Br-BETA, which can be labeled with 75 Br (T 1/2 = 97 min), 76 Br (T 1/2 = 16 h), or 77 Br (T 1/2 = 3.2 days), could be developed as potential PET radiotracer for Aβ plaques with longer physical half-life options [ 29 ].…”

“…Sodium iodide, [ 124 I]NaI (3D Imaging LLC) and [ 125 I]NaI (ARC Inc.) were used to prepare [ 124 I]IBETA and [ 125 I]IBETA by the electrophilic substitution of the tributyltin derivative using reported radioiodination methods [ 21 , 22 ]. The radiosynthesis of [ 124 I]IBETA using methods modified from [ 22 ] and [ 125 I]IBETA using methods modified from [ 15 , 16 ] were successfully caried out. Then, 0.1 mL H 2 O 2 (3%) was added to a mixture of 0.1 mL of tributyltin derivative (1 mg/0.2 mL of ethanol), 21 MBq NaI 124 , and 0.1 mL of 1N HCl in a sealed vial.…”

“…Since the heteroatoms in the "azo" functionality of [ 11 C]TAZA (Figure 1) result in a higher affinity to Aβ plaques and lower white matter binding in postmortem human AD brain slices in comparison to [ 11 C]PiB, a fluorine-18 analog of [ 11 C]TAZA-[ 18 F]Flotaza (Figure 1)-has recently been developed and evaluated for Aβ plaque imaging [14,15]. [ 18 F]Flotaza yielded significantly higher binding in the gray matter regions where Aβ plaques were located by anti-Aβ immunostains, compared to [ 11 C]TAZA.…”

“…[ 18 F]Flotaza yielded significantly higher binding in the gray matter regions where Aβ plaques were located by anti-Aβ immunostains, compared to [ 11 C]TAZA. Additionally, [ 18 F]Flotaza showed a higher gray matter to white matter ratio than [ 18 F]Florbetaben, a close fluoropegylated analog of [ 11 C]Dalene (Figure 1), which exhibited a low amount of gray matter binding [15]. ]Dalene (Figure 1), which exhibited a low amount of gray matter binding [15].…”

“…Additionally, [ 18 F]Flotaza showed a higher gray matter to white matter ratio than [ 18 F]Florbetaben, a close fluoropegylated analog of [ 11 C]Dalene (Figure 1), which exhibited a low amount of gray matter binding [15]. ]Dalene (Figure 1), which exhibited a low amount of gray matter binding [15].…”