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

Autor: Helbert, Hugo, Ploeg, Emily M., Samplonius, Douwe F., Blok, Simon N., Antunes, Ines F., Böhmer, Verena I., Luurtsema, Gert, Dierckx, Rudi A. J. O., Feringa, Ben L., Elsinga, Philip H., Szymanski, Wiktor, Helfrich, Wijnand
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Zdroj: EJNMMI Radiopharmacy & Chemistry; 3/3/2022, Vol. 7 Issue 1, p1-11, 11p
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 89Zr-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 18F-PET tracer and tumor markers. Results: A copper(I)-catalysed click reaction-based radiolabeling protocol was developed for the synthesis of fluorescein-derived molecule [18F]TPF. Binding of [18F]TPF on FITC-bearing bsAbs was confirmed. An in vitro autoradiography assay demonstrated that [18F]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 18F-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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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