The development of
novel ligands for G-protein-coupled receptors
(GPCRs) typically entails the characterization of their binding affinity,
which is often performed with radioligands in a competition or saturation
binding assay format. Since GPCRs are transmembrane proteins, receptor
samples for binding assays are prepared from tissue sections, cell
membranes, cell homogenates, or intact cells. As part of our investigations
on modulating the pharmacokinetics of radiolabeled peptides for improved
theranostic targeting of neuroendocrine tumors with a high abundance
of the somatostatin receptor sub-type 2 (SST2), we characterized
a series of64Cu-labeled [Tyr3]octreotate (TATE)
derivatives in vitro in saturation binding assays. Herein, we report
on the SST2binding parameters measured toward intact mouse
pheochromocytoma cells and corresponding cell homogenates and discuss
the observed differences taking the physiology of SST2and
GPCRs in general into account. Furthermore, we point out method-specific
advantages and limitations.