Comparison of ¹¹¹In-DOTA-NOC and ¹¹¹In-DOTA-TATE Distribution in the Target and Dose-limiting Tissues: Conflicting Results In Vitro and In Vivo

Abstract

Background: In this study, some important biological characteristics of two radiolabelled somatostatin analogues ¹¹¹In-DOTA-1-Nal³-octreotide (DOTA-NOC) and ¹¹¹In-DOTA-Tyr³-octreotate (DOTA-TATE) were compared. Materials and Methods: Rats were used for in vivo biodistribution experiments and in vitro cell models (OK and AR42J cell lines) were used for simulating the internalization in the kidney and in subtype 2 somatostatin receptor (SSTR2)-positive tissues, respectively. Results: Significantly higher radioactivity concentrations in rat organs with high density of somatostatin receptors after ¹¹¹In-DOTA-NOC administration in comparison with ¹¹¹In-DOTA-TATE were observed. The predominant urine excretion was associated with accumulation of the radioactivity in the kidney, where higher retention of ¹¹¹In-DOTA-TATE compared to ¹¹¹In-DOTA-NOC was detected. In the OK cell line the opposite results were found. No significant differences in the in vitro internalization and externalization of radioactivity to AR42J cell line were found for either peptide suggesting their same affinity for SSTR2. Conclusion: Preclinical experiments indicated that ¹¹¹In-DOTA-NOC is a very promising peptide for somatostatin receptor-positive tumour visualization. The conflict between the in vitro and in vivo kidney handling showed that the transfer of results from in vitro to in vivo conditions and their interpretation should be performed very carefully because both types of experiments can be affected by different factors, making their simple comparison difficult.