Download The possible role of somatropin derivatives as a theranostic in

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.