Receptor Affinity and Preclinical Biodistribution of Radiolabeled Somatostatin Analogs

In this study, we investigated the relationship between affinity to somatostatin receptor subtype2 (SSTR2) and uptake of radioactivity from a group of radiolabeled somatostatin analogues in somatostatin receptor-rich tissues of rats. Organs with a high density of somatostin receptors (namely the adrenals and pancreas bearing mainly SSTR2; this receptor subtype is also the most abundant in somatostatin receptor-positive tumors) were chosen as markers of specific binding of the peptides in vivo. Accumulations of radioactivity in these organs 24 h and 48 h after intravenous administration of six In-111-labeled octreotide and octreotate derivatives with predominant affinity to SSTR2 were correlated with affinity to SSTR2, determined in vitro (IC50 values). For correlation between adrenal uptake of radioactivity and IC50, the best fit for exponential dependence was found; for that of pancreas, however, linear dependence was the most suitable. In cases where the values for the peptide with affinity to SSTR subtypes 2, 3 and 5, namely In-111- DOTA-Nal(3)-octreotide were included in the group of studied agents, substantially less correlations were obtained. Our results showed that uptake of radioactivity in tissues with a high density of somatostatin receptors correlates with somatostatin receptor affinity of receptor-specific peptides; however, other factors (the affinity to particular receptor subtypes, the overall pharmacokinetic profile in the body etc.) may contribute to this observed relationship.