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

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., F-18). In recent years, new reactions have appeared for the F-18-labeling of agents that are difficult to access by applying traditional radiochemistry, for example those requiring F-18 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 F-18-labeling methodologies within automated modules. Here, we describe the workflow that led to the automated radiosynthesis of the poly(ADP-ribose) polymerase (PARP) inhibitor [F-18]olaparib. First, we established a robust manual protocol to prepare [F-18]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 (A(m)) up to 34.6 GBq/mu mol. Automation of the process, consisting of copper-mediated F-18-fluorodeboronation followed by deprotection, was achieved on an Eckert & Ziegler Modular-Lab radiosynthesis platform, affording [F-18]olaparib in a 6% +/- 5% (n = 3; synthesis time, 120 min) NDC activity yield with A(m) up to 319 GBq/mu mol. Automation of new methods for F-18 incorporation into unactivated (hetero)arenes for translation to the clinic has progressed slowly. This protocol describes a workflow leading to automated radiosynthesis of the PARP inhibitor [F-18]olaparib.