Synthesis, Radiolabeling, and In Vivo Pharmacokinetic Evaluation of the Amyloid Beta Radioligand [11C]AZD4694 in Nonhuman Primates
Tóm tắt
[18F]AZD4694 (2-(2-18F-fluoro-6-(methylamino)-3-pyridyl)benzofuran-5-ol) is a radioligand suitable for imaging of amyloid beta deposits in the living human brain using positron emission tomography (PET). Here, we report the preparation and pharmacokinetic profile of its carbon-11 (t
1/2
= 20.4 min) labeled isotopolog [11C]AZD4694 and compare [11C]AZD4694 with the hitherto most widely applied amyloid PET radioligand [11C]Pittsburgh Compound B (PiB). The immediate unlabeled precursor to [11C]AZD4694 was prepared in a four-step convergent synthesis. Subsequent N-11C-methylation of this precursor with [11C]methyl iodide yielded [11C]AZD4694, which after isolation and formulation was injected into cynomolgus monkeys. The radioactivity in nonhuman primate brain following injection of [11C]AZD4694 and [11C]PiB was measured using PET. [11C]AZD4694 was prepared in a 60 % incorporation yield. In a head to head comparison with [11C]PiB, it appeared that [11C]AZD4694 displayed slightly lower nonspecific binding in white matter than [11C]PiB as well as more rapid pharmacokinetics in the brain. The advantageous pharmacokinetic profile and low nonspecific binding render [11C]AZD4694 a promising PET radioligand for imaging of amyloid beta in the human brain with PET.
Tài liệu tham khảo
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