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The possible role of somatropin derivatives as a theranostic in oncology Nathalie Bracke1, Evelien Wynendaele1, Sophia Barhdadi1, Christoph Van de Wiele2 and Bart De Spiegeleer1,* 1 DruQuaR (Drug Quality & Registration) group, Faculty of Pharmaceutical Sciences, Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium. *[email protected] 2 Department of Nuclear Medicine, Ghent University Hospital, 9000 Ghent, Belgium (O. Ref/ 2013-385a) Somatropin (i.e. recombinant human growth hormone, rhGH) is a biologic drug, approved to treat growth hormone deficiencies and is available as originator drug and biosimilar, but also as SFFCs (spurious/falsely-labelled/falsified/counterfeit). Somatropin can perform its actions by binding with high affinity to the extracellular domains of two identical molecules of human growth hormone receptors (hGHR), which are widely expressed in liver tissue, but are also aberrantly overexpressed in numerous cancers such as prostate, breast and colon cancer. The potential involvement of the GH-system in tumor promotion and progression, as well as the internalization of the receptor-ligand complex, makes hGHR a potential tumor target for the development of somatropin-based (radio-)pharmaceuticals. Modifications with chelating agents like S-2-(4-isothiocyanatobenzyl)-1,4,7triazacyclononane-1,4,7-triacetic acid (NOTA) allows the incorporation of radiometals for SPECT/PET-diagnostic or therapeutic purposes. However, because somatropin has nine potential binding sites (Lys) for NOTA, analytical characterization of the heterogeneous production is crucial as chemical modification can influence the functional quality upon receptor binding and hence, the outcome of biological assays. Chromatographic techniques were used to profile the modified somatropins. Their binding characteristics (i.e. affinity (KD) and kinetics (kon and koff)) were monitored by hGHAb, hGHR and cells using Surface Acoustic Wave (SAW) biosensor. Moreover, somatropin-derived peptides were evaluated as well for their binding potential using SAW. The synthesis of somatropin derivatives, including peptides, are potential scaffolds for the development of target-specific (radio-)pharmaceuticals towards diagnosis, patient-sensitivity (personalized medicine) and treatment of growth hormone-specific cancers.