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Interest in quantifying metal-Aβ species in vivo led to the synthesis and evaluation of [ 11 C]L2-b and [ 18 F]FL2-b as radiopharmaceuticals for studying the metallobiology of Alzheimer's disease (AD) using positron emission tomography (PET) imaging. [ 11 C]L2-b was synthesized in 3.6% radiochemical yield (nondecay corrected, n = 3), &gt;95% radiochemical purity, from the corresponding desmethyl precursor. [ 18 F]FL2-b was synthesized in 1.0% radiochemical yield (nondecay corrected, n = 3), &gt;99% radiochemical purity, from a 6-chloro pyridine precursor. Autoradiography experiments with AD positive and healthy control brain samples were used to determine the specificity of binding for the radioligands compared to [ 11 C]PiB, a known imaging agent for β-amyloid (Aβ) aggregates. The K  d for [ 11 C]L2-b and [ 18 F]FL2-b were found to be 3.5 and 9.4 nM, respectively, from those tissue studies. Displacement studies of [ 11 C]L2-b and [ 18 F]FL2-b with PiB and AV-45 determined that L2-b binds to Aβ aggregates differently from known radiopharmaceuticals. Finally, brain uptake of [ 11 C]L2-b was examined through microPET imaging in healthy rhesus macaque, which revealed a maximum uptake at 2.5 min (peak SUV = 2.0) followed by rapid egress ( n = 2).

Targeting Metal-Aβ Aggregates with Bifunctional Radioligand [11C]L2-b and a Fluorine-18 Analogue [18F]FL2-b

Targeting Metal-Aβ Aggregates with Bifunctional Radioligand [¹¹C]L2-b and a Fluorine-18 Analogue [¹⁸F]FL2-b