Synthesis and characterization of a novel [52Mn]Mn-labelled affibody based radiotracer for HER2+ targeting

• Published in: Inorganic chemistry frontiers 2023-08, Vol.10 (16), p.4734-4745
• Main Authors: Váradi, Balázs, Brezovcsik, Károly, Garda, Zoltán, Madarasi, Enikő, Szedlacsek, Horea, Badea, Rodica-Aura, Andrei-Mihai Vasilescu, Adina-Gabriela Puiu, Ionescu, Aura Elena, Livia-Elena Sima, Munteanu, Cristian V A, Călăraş, Simona, Vágner, Adrienn, Szikra, Dezső, Toàn, Ngô Minh, Nagy, Tibor, Szűcs, Zoltán, Szedlacsek, Stefan, Nagy, Gábor, Tircsó, Gyula
• Format: Article
• Language: English
• Subjects: Conjugates; Conjugation; High performance liquid chromatography; In vivo methods and tests; Inorganic chemistry; Magnetic resonance imaging; Manganese isotopes; Medical imaging; Positron emission; Radioactive tracers; Synthesis; Tumors
• ISSN: 2052-1545; 2052-1553
• DOI: 10.1039/d3qi00356f

Targeted molecular imaging is a valuable method in cancer diagnosis. The palette of manganese isotopes provides an excellent opportunity for bimodal imaging, given that it possesses a long-lived positron-emitting isotope usable in functional Positron Emission Tomography (PET) imaging (52Mn), while the paramagnetic nature of 55Mn makes monoaquated complexes of Mn(ii) suitable for Magnetic Resonance Imaging (MRI). Present study reports on the synthesis of series of new model bifunctional Mn(II) chelators (BFC) derived from the rigid 3,9-PC2A ligand and on the studies of physicochemical properties of their Mn(II) chelates. From these, the 3,9-PC2ABnpCO2H platform was selected for bioconjugation and for further in vivo studies. Anti-HER2 affibody was used as a highly specific binding protein, which was expressed in a prokaryotic system, purified by affinity chromatography followed by RP-HPLC. The specificity of the affibody for HER2 receptors was proved following its conjugation with AlexaFluor555 dye. Finally the affibody was conjugated with the selected 3,9-PC2ABnpCO2H BFC and [52Mn]Mn(ii) labelling was performed. The labelled conjugate was tested in a pilot study by PET imaging using MDA-MB (HER2+) and 4T1 (HER2−) tumour-bearing mice. The results demonstrate that the [[52Mn]Mn(3,9-PC2ABnpMA)(H2O)]-Cys-HER2-affibody conjugate is an efficient and specific molecular vehicle for targeting and visualizing HER2+ tumours by 52Mn-based PET imaging.