Evaluation of affinity matured Affibody molecules for imaging of the immune checkpoint protein B7-H3

Dades bibliogràfiques
Parent link:Nuclear Medicine and Biology.— .— Amsterdam: Elsevier Science Publishing Company Inc.
Vol. 124-125.— 2023.— Article number 108384, 11 p.
Altres autors: Oroujeni M. Maryam, Bezverkhniaia E. A. Ekaterina Aleksandrovna, Xu Tianqi, Liu Yongsheng, Plotnikov E. V. Evgeny Vladimirovich, Klint S. Susanne, Ryer E. Eva, Karlberg I. Ida, Orlova A. M. Anna Markovna, Frejd F. Y. Fredrik, Tolmachev V. M. Vladimir Maksimilianovich
Sumari:Title screen
B7-H3 (CD276), an immune checkpoint protein, is a promising molecular target for immune therapy of malignant tumours. Sufficient B7-H3 expression level is a precondition for successful therapy. Radionuclide molecular imaging is a powerful technique for visualization of expression levels of molecular targets in vivo. Use of small radiolabelled targeting proteins would enable high-contrast radionuclide imaging of molecular targets if adequate binding affinity and specificity of an imaging probe could be provided. Affibody molecules, small engineered affinity proteins based on a non-immunoglobulin scaffold, have demonstrated an appreciable potential in radionuclide imaging. Proof-of principle of radionuclide visualization of expression levels of B7-H3 in vivo was demonstrated using the [99mTc]Tc-AC12-GGGC Affibody molecule. We performed an affinity maturation of AC12, enabling selection of clones with higher affinity. Three most promising clones were expressed with a –GGGC (triglycine-cysteine) chelating sequence at the C-terminus and labelled with technetium-99m (99mTc). 99mTc-labelled conjugates bound to B7-H3-expressing cells specifically in vitro and in vivo. Biodistribution in mice bearing B7-H3-expressing SKOV-3 xenografts demonstrated improved imaging properties of the new conjugates compared with the parental variant [99mTc]Tc-AC12-GGGC. [99mTc]Tc-SYNT-179 provided the strongest improvement of tumour-to-organ ratios. Thus, affinity maturation of B7-H3 Affibody molecules could improve biodistribution and targeting properties for imaging of B7-H3-expressing tumours
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AM_Agreement
Idioma:anglès
Publicat: 2023
Matèries:
Accés en línia:https://doi.org/10.1016/j.nucmedbio.2023.108384
Format: Electrònic Capítol de llibre
KOHA link:https://koha.lib.tpu.ru/cgi-bin/koha/opac-detail.pl?biblionumber=683368

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