Manual and automated Cu-mediated radiosynthesis of the PARP inhibitor [18F]olaparib

Florian Guibbal, Patrick G. Isenegger, Thomas C. Wilson, Anna Pacelli, Damien Mahaut, Jeroen Sap, Nichloas J. Taylor, Stefan Verhoog, Sean Preshlock, Rebekka Hueting, Bart Cornelissen, Véronique Gouverneur

Research output: Contribution to journalArticlepeer-review

Abstract

Positron emission tomography (PET) is a diagnostic nuclear imaging modality that relies on automated protocols to prepare agents labeled with a positron-emitting radionuclide (e.g., 18F). In recent years, new reactions have appeared for the 18F-labeling of agents that are difficult to access by applying traditional radiochemistry, for example those requiring 18F incorporation into unactivated (hetero)arenes. However, automation of these new methods for translation to the clinic has progressed slowly because extensive modification of manual protocols is typically required when implementing novel 18F-labeling methodologies within automated modules. Here, we describe the workflow that led to the automated radiosynthesis of the poly(ADP-ribose) polymerase (PARP) inhibitor [18F]olaparib. First, we established a robust manual protocol to prepare [18F]olaparib from the protected N-[2-(trimethylsilyl)ethoxy]methyl (SEM) arylboronate ester precursor in a 17% ± 5% (n = 15; synthesis time, 135 min) non-decay-corrected (NDC) activity yield, with molar activity (Am) up to 34.6 GBq/µmol. Automation of the process, consisting of copper-mediated 18F-fluorodeboronation followed by deprotection, was achieved on an Eckert & Ziegler Modular-Lab radiosynthesis platform, affording [18F]olaparib in a 6% ± 5% (n = 3; synthesis time, 120 min) NDC activity yield with Am up to 319 GBq/µmol.
Original languageEnglish
Pages (from-to)1525 - 1541
Number of pages17
JournalNature Protocols
Volume15
Issue number4
DOIs
Publication statusPublished - 28 Feb 2020

Keywords

  • Automation
  • Chemical modification
  • Synthetic chemistry methodology
  • Positron-Emission Tomography
  • Sensors and probes

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