Modular Medical Imaging Agents Based on Azide-Alkyne Huisgen Cycloadditions: Synthesis and Pre-Clinical Evaluation of 18 F-Labeled PSMA-Tracers for Prostate Cancer Imaging.

Autor: Böhmer VI; Department of Nuclear Medicine and Molecular Imaging, Department of Radiology, Department of Surgical Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.; Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 4, 9747 AF, Groningen, The Netherlands., Szymanski W; Department of Nuclear Medicine and Molecular Imaging, Department of Radiology, Department of Surgical Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.; Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 4, 9747 AF, Groningen, The Netherlands., van den Berg KO; Department of Nuclear Medicine and Molecular Imaging, Department of Radiology, Department of Surgical Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands., Mulder C; Department of Nuclear Medicine and Molecular Imaging, Department of Radiology, Department of Surgical Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands., Kobauri P; Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 4, 9747 AF, Groningen, The Netherlands., Helbert H; Department of Nuclear Medicine and Molecular Imaging, Department of Radiology, Department of Surgical Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.; Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 4, 9747 AF, Groningen, The Netherlands., van der Born D; FutureChemistry, Toernooiveld 100, 6525 EC, Nijmegen, The Netherlands., Reeβing F; Department of Nuclear Medicine and Molecular Imaging, Department of Radiology, Department of Surgical Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.; Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 4, 9747 AF, Groningen, The Netherlands., Huizing A; Department of Nuclear Medicine and Molecular Imaging, Department of Radiology, Department of Surgical Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.; Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 4, 9747 AF, Groningen, The Netherlands., Klopstra M; Syncom, Kadijk 3, 9747 AT, Groningen, The Netherlands., Samplonius DF; Department of Nuclear Medicine and Molecular Imaging, Department of Radiology, Department of Surgical Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands., Antunes IF; Department of Nuclear Medicine and Molecular Imaging, Department of Radiology, Department of Surgical Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands., Sijbesma JWA; Department of Nuclear Medicine and Molecular Imaging, Department of Radiology, Department of Surgical Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands., Luurtsema G; Department of Nuclear Medicine and Molecular Imaging, Department of Radiology, Department of Surgical Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands., Helfrich W; Department of Nuclear Medicine and Molecular Imaging, Department of Radiology, Department of Surgical Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands., Visser TJ; Syncom, Kadijk 3, 9747 AT, Groningen, The Netherlands., Feringa BL; Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 4, 9747 AF, Groningen, The Netherlands., Elsinga PH; Department of Nuclear Medicine and Molecular Imaging, Department of Radiology, Department of Surgical Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Jazyk: angličtina
Zdroj: Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2020 Aug 21; Vol. 26 (47), pp. 10871-10881. Date of Electronic Publication: 2020 Jul 21.
DOI: 10.1002/chem.202001795
Abstrakt: Since the seminal contribution of Rolf Huisgen to develop the [3+2] cycloaddition of 1,3-dipolar compounds, its azide-alkyne variant has established itself as the key step in numerous organic syntheses and bioorthogonal processes in materials science and chemical biology. In the present study, the copper(I)-catalyzed azide-alkyne cycloaddition was applied for the development of a modular molecular platform for medical imaging of the prostate-specific membrane antigen (PSMA), using positron emission tomography. This process is shown from molecular design, through synthesis automation and in vitro studies, all the way to pre-clinical in vivo evaluation of fluorine-18- labeled PSMA-targeting 'F-PSMA-MIC' radiotracers (t 1/2 =109.7 min). Pre-clinical data indicate that the modular PSMA-scaffold has similar binding affinity and imaging properties to the clinically used [ 68 Ga]PSMA-11. Furthermore, we demonstrated that targeting the arene-binding in PSMA, facilitated through the [3+2]cycloaddition, can improve binding affinity, which was rationalized by molecular modeling. The here presented PSMA-binding scaffold potentially facilitates easy coupling to other medical imaging moieties, enabling future developments of new modular imaging agents.
(© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)
Databáze: MEDLINE
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