TY - JOUR
T1 - Manual and automated Cu-mediated radiosynthesis of the PARP inhibitor [18F]olaparib
AU - Guibbal, Florian
AU - Isenegger, Patrick G.
AU - Wilson, Thomas C.
AU - Pacelli, Anna
AU - Mahaut, Damien
AU - Sap, Jeroen
AU - Taylor, Nichloas J.
AU - Verhoog, Stefan
AU - Preshlock, Sean
AU - Hueting, Rebekka
AU - Cornelissen, Bart
AU - Gouverneur, Véronique
N1 - Funding Information:
We acknowledge financial support from the Medical Research Council (MRC MR/R01695X/1, F.G. and A.P.), the Engineering and Physical Sciences Research Council (EPSRC EP/N509711/1, EP/L025604/1, J.B.I.S. and S.P.) and the Biotechnology and Biological Sciences Research Council (BBSRC BB/ K01191X/1; N.J.T. and P.G.I.). This work was also supported by the Cancer Research UK (CRUK C5255/A16466, T.C.W. and S.V.), Pfizer, UCB, and the Swiss National Science Foundation (P2BSP2_178609, P.G.I.). We thank T. C. Wilson for providing the copper complex.
Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2020/2/28
Y1 - 2020/2/28
N2 - 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.
AB - 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.
KW - Automation
KW - Chemical modification
KW - Synthetic chemistry methodology
KW - Positron-Emission Tomography
KW - Sensors and probes
UR - http://www.scopus.com/inward/record.url?scp=85080148647&partnerID=8YFLogxK
U2 - 10.1038/s41596-020-0295-7
DO - 10.1038/s41596-020-0295-7
M3 - Article
SN - 1754-2189
VL - 15
SP - 1525
EP - 1541
JO - Nature Protocols
JF - Nature Protocols
IS - 4
ER -