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01-04-2014 | Brief Article

Synthesis, Radiolabeling, and In Vivo Pharmacokinetic Evaluation of the Amyloid Beta Radioligand [¹¹C]AZD4694 in Nonhuman Primates

Authors: Magnus Schou, Katarina Varnäs, Johan Sandell, Peter Johnström, Zsolt Cselenyi, Samuel Svensson, Ryuji Nakao, Nahid Amini, Linda Bergman, Anna Sumic, Balazs Gulyas, Eva Lindström-Böö, Christer Halldin, Lars Farde

Published in: Molecular Imaging and Biology | Issue 2/2014

Abstract

Purpose

[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).

Procedures

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.

Results

[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.

Conclusions

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.

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Title: Synthesis, Radiolabeling, and In Vivo Pharmacokinetic Evaluation of the Amyloid Beta Radioligand [11C]AZD4694 in Nonhuman Primates
Authors: Magnus Schou
Katarina Varnäs
Johan Sandell
Peter Johnström
Zsolt Cselenyi
Samuel Svensson
Ryuji Nakao
Nahid Amini
Linda Bergman
Anna Sumic
Balazs Gulyas
Eva Lindström-Böö
Christer Halldin
Lars Farde
Publication date: 01-04-2014
Publisher: Springer US
Published in: Molecular Imaging and Biology / Issue 2/2014
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-013-0666-3

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Synthesis, Radiolabeling, and In Vivo Pharmacokinetic Evaluation of the Amyloid Beta Radioligand [¹¹C]AZD4694 in Nonhuman Primates

Abstract

Purpose

Procedures

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Procedures

Results

Conclusions

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