A proof-of-concept study on the use of a fluorescein-based 18 F-tracer for pretargeted PET.

Autor: Helbert H; Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 4, 9747, Groningen, The Netherlands.; Department of Nuclear Medicine and Molecular Imaging, Medical Imaging Center, University of Groningen, UMC Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands., Ploeg EM; Department of Surgery, Translational Surgical Oncology, University of Groningen, UMC Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands., Samplonius DF; Department of Surgery, Translational Surgical Oncology, University of Groningen, UMC Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands., Blok SN; Department of Nuclear Medicine and Molecular Imaging, Medical Imaging Center, University of Groningen, UMC Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands., Antunes IF; Department of Nuclear Medicine and Molecular Imaging, Medical Imaging Center, University of Groningen, UMC Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands., Böhmer VI; Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 4, 9747, Groningen, The Netherlands.; Department of Nuclear Medicine and Molecular Imaging, Medical Imaging Center, University of Groningen, UMC Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands., Luurtsema G; Department of Nuclear Medicine and Molecular Imaging, Medical Imaging Center, University of Groningen, UMC Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands., Dierckx RAJO; Department of Nuclear Medicine and Molecular Imaging, Medical Imaging Center, University of Groningen, UMC Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands., Feringa BL; Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 4, 9747, Groningen, The Netherlands., Elsinga PH; Department of Nuclear Medicine and Molecular Imaging, Medical Imaging Center, University of Groningen, UMC Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands. p.h.elsinga@umcg.nl., Szymanski W; Department of Radiology, Medical Imaging Center, University of Groningen, UMC Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands. w.szymanski@umcg.nl., Helfrich W; Department of Surgery, Translational Surgical Oncology, University of Groningen, UMC Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Jazyk: angličtina
Zdroj: EJNMMI radiopharmacy and chemistry [EJNMMI Radiopharm Chem] 2022 Mar 03; Vol. 7 (1), pp. 3. Date of Electronic Publication: 2022 Mar 03.
DOI: 10.1186/s41181-022-00155-2
Abstrakt: Background: Pretargeted immuno-PET tumor imaging has emerged as a valuable diagnostic strategy that combines the high specificity of antibody-antigen interaction with the high signal and image resolution offered by short-lived PET isotopes, while reducing the irradiation dose caused by traditional 89 Zr-labelled antibodies. In this work, we demonstrate proof of concept of a novel 'two-step' immuno-PET pretargeting approach, based on bispecific antibodies (bsAbs) engineered to feature dual high-affinity binding activity for a fluorescein-based 18 F-PET tracer and tumor markers.
Results: A copper(I)-catalysed click reaction-based radiolabeling protocol was developed for the synthesis of fluorescein-derived molecule [ 18 F]TPF. Binding of [ 18 F]TPF on FITC-bearing bsAbs was confirmed. An in vitro autoradiography assay demonstrated that [ 18 F]TPF could be used for selective imaging of EpCAM-expressing OVCAR3 cells, when pretargeted with EpCAMxFITC bsAb. The versatility of the pretargeting approach was showcased in vitro using a series of fluorescein-binding bsAbs directed at various established cancer-associated targets, including the pan-carcinoma cell surface marker EpCAM, EGFR, melanoma marker MCSP (aka CSPG4), and immune checkpoint PD-L1, offering a range of potential future applications for this pretargeting platform.
Conclusion: A versatile pretargeting platform for PET imaging, which combines bispecific antibodies and a fluorescein-based 18 F-tracer, is presented. It is shown to selectively target EpCAM-expressing cells in vitro and its further evaluation with different bispecific antibodies demonstrates the versatility of the approach.
(© 2022. The Author(s).)
Databáze: MEDLINE
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