Direct Cu-mediated aromatic18F-labeling of highly reactive tetrazines for pretargeted bioorthogonal PET imaging
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Direct Cu-mediated aromatic18F-labeling of highly reactive tetrazines for pretargeted bioorthogonal PET imaging. / García-Vázquez, Rocío; Battisti, Umberto M.; Jørgensen, Jesper T.; Shalgunov, Vladimir; Hvass, Lars; Stares, Daniel L.; Petersen, Ida N.; Crestey, François; Löffler, Andreas; Svatunek, Dennis; Kristensen, Jesper L.; Mikula, Hannes; Kjaer, Andreas; Herth, Matthias M.
I: Chemical Science, Bind 12, Nr. 35, 2021, s. 11668-11675.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Direct Cu-mediated aromatic18F-labeling of highly reactive tetrazines for pretargeted bioorthogonal PET imaging
AU - García-Vázquez, Rocío
AU - Battisti, Umberto M.
AU - Jørgensen, Jesper T.
AU - Shalgunov, Vladimir
AU - Hvass, Lars
AU - Stares, Daniel L.
AU - Petersen, Ida N.
AU - Crestey, François
AU - Löffler, Andreas
AU - Svatunek, Dennis
AU - Kristensen, Jesper L.
AU - Mikula, Hannes
AU - Kjaer, Andreas
AU - Herth, Matthias M.
PY - 2021
Y1 - 2021
N2 - Pretargeted imaging can be used to visualize and quantify slow-accumulating targeting vectors with short-lived radionuclides such as fluorine-18 - the most popular clinically applied Positron Emission Tomography (PET) radionuclide. Pretargeting results in higher target-to-background ratios compared to conventional imaging approaches using long-lived radionuclides. Currently, the tetrazine ligation is the most popular bioorthogonal reaction for pretargeted imaging, but a direct18F-labeling strategy for highly reactive tetrazines, which would be highly beneficial if not essential for clinical translation, has thus far not been reported. In this work, a simple, scalable and reliable direct18F-labeling procedure has been developed. We initially studied the applicability of different leaving groups and labeling methods to develop this procedure. The copper-mediated18F-labeling exploiting stannane precursors showed the most promising results. This approach was then successfully applied to a set of tetrazines, including highly reactive H-tetrazines, suitable for pretargeted PET imaging. The labeling succeeded in radiochemical yields (RCYs) of up to approx. 25%. The new procedure was then applied to develop a pretargeting tetrazine-based imaging agent. The tracer was synthesized in a satisfactory RCY ofca.10%, with a molar activity of 134 ± 22 GBq μmol−1and a radiochemical purity of >99%. Further evaluation showed that the tracer displayed favorable characteristics (target-to-background ratios and clearance) that may qualify it for future clinical translation.
AB - Pretargeted imaging can be used to visualize and quantify slow-accumulating targeting vectors with short-lived radionuclides such as fluorine-18 - the most popular clinically applied Positron Emission Tomography (PET) radionuclide. Pretargeting results in higher target-to-background ratios compared to conventional imaging approaches using long-lived radionuclides. Currently, the tetrazine ligation is the most popular bioorthogonal reaction for pretargeted imaging, but a direct18F-labeling strategy for highly reactive tetrazines, which would be highly beneficial if not essential for clinical translation, has thus far not been reported. In this work, a simple, scalable and reliable direct18F-labeling procedure has been developed. We initially studied the applicability of different leaving groups and labeling methods to develop this procedure. The copper-mediated18F-labeling exploiting stannane precursors showed the most promising results. This approach was then successfully applied to a set of tetrazines, including highly reactive H-tetrazines, suitable for pretargeted PET imaging. The labeling succeeded in radiochemical yields (RCYs) of up to approx. 25%. The new procedure was then applied to develop a pretargeting tetrazine-based imaging agent. The tracer was synthesized in a satisfactory RCY ofca.10%, with a molar activity of 134 ± 22 GBq μmol−1and a radiochemical purity of >99%. Further evaluation showed that the tracer displayed favorable characteristics (target-to-background ratios and clearance) that may qualify it for future clinical translation.
UR - http://europepmc.org/abstract/med/34659701
U2 - 10.1039/d1sc02789a
DO - 10.1039/d1sc02789a
M3 - Journal article
C2 - 34659701
AN - SCOPUS:85115162973
VL - 12
SP - 11668
EP - 11675
JO - Chemical Science
JF - Chemical Science
SN - 2041-6520
IS - 35
ER -
ID: 281602615