A concise radiosynthesis of the tau radiopharmaceutical, [18F]T807. (24th July 2013)

• Record Type: Journal Article
• Authors: Shoup, Timothy M.; Yokell, Daniel L.; Rice, Peter A.; Jackson, Raul N.; Livni, Eli; Johnson, Keith A.; Brady, Thomas J.; Vasdev, Neil
• Is Part Of: Journal of labelled compounds & radiopharmaceuticals. Volume 56:Number 14(2013)
• Page Start: 736
• Page End: 740
• Publication Date: 2013-07-24
• Subjects: Tracers (Chemistry) -- Periodicals; Radiopharmaceuticals -- Periodicals; 615.8424
• DOI: 10.1002/jlcr.3098
• Languages: English
• ISSNs: 0362-4803

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Fluorine‐18 labeled 7‐(6‐fluoropyridin‐3‐yl)‐5H‐pyrido[4, 3‐b]indole ([<sup>18</sup>F]T807) is a potent and selective agent for imaging paired helical filaments of tau and is among the most promising PET radiopharmaceuticals for this target in early clinical trials. The present study reports a simplified one‐step method for the synthesis of [<sup>18</sup>F]T807 that is broadly applicable for routine clinical production using a GE TRACERlab™ FX<sub>FN</sub> radiosynthesis module. Key facets of our optimized radiosynthesis include development and use of a more soluble protected precursor, <italic>tert</italic>‐butyl 7‐(6‐nitropyridin‐3‐yl)‐5H‐pyrido[4, 3‐b]indole‐5‐carboxylate, as well as new HPLC separation conditions that enable a facile one‐step synthesis. During the nucleophilic fluorinating reaction with potassium cryptand [<sup>18</sup>F]fluoride (K[<sup>18</sup>F]/K<sub>222</sub>) in DMSO at 130 °C over 10 min the precursor is concurrently deprotected. Formulated [<sup>18</sup>F]T807 was prepared in an uncorrected radiochemical yield of 14 ± 3%, with a specific activity of 216 ± 60 GBq/µmol (5837 ± 1621 mCi/µmol) at the end of synthesis (60 min; <italic>n</italic> = 3) and validated for human use. This methodology offers the advantage of faster synthesis in fewer steps, with simpler automation that we anticipate will facilitate widespread clinical use of [<sup>18</sup>F]T807. Copyright © 2013 John Wiley & Sons, Ltd.</p> </abstract>