Radiolabelling of Glucose-Tyr³-octreotate with 125I and Analysis of Its Metabolism in Rats: Comparison with Radiolabelled DOTA-Tyr³-octreotate

Abstract

Background: Somatostatin analogues labelled with radiometals or radiohalogens are useful for the imaging and treatment of somatostatin receptor-containing tumours. In this study, the procedures for the radioiodination of glucose-Tyr³-octreotate (gluc-Tyr³-tate) and radiolabelling of DOTA-Tyr³-octreotate (DOTA-Tyr³-tate) with ¹¹¹In, ¹⁷⁷Lu and ¹²⁵I were compared and their metabolism in rats was analyzed. The usefulness of high performance liquid chromatography (HPLC) analysis and instant thin-layer chromatography on silica gel (ITLC-SG) for both radiochemical purity determination and analysis of metabolism in urine was investigated. Materials and Methods: For labelling with radiometals, the formation of a complex with the 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) functionality of the peptide was employed. Radioiodination was performed by the chloramime-T method. The radiochemical purity of radiolabelled peptides and the analyses of rat urine were determined by HPLC and/or ITLC-SG methods. Male Wistar rats were used in the elimination studies. Results: DOTA-Tyr³-tate was simply radiolabelled with radiometals with high yield and high radiochemical purity. Stopping of the reaction was a critical step for radioiodination, therefore labelling of gluc-Tyr³-tate and DOTA-Tyr³-tate with ¹²⁵I was not so simple and the reaction product had to be purified by preparative HPLC analysis. Whereas ¹¹¹In-DOTA-Tyr³-tate and ¹⁷⁷Lu-DOTA-Tyr³-tate were eliminated in rat urine in a practically unchanged form, a significant proportion of metabolites was observed with radioiodinated peptides, particularly at longer time intervals. Conclusion: Labelling of DOTA-Tyr³-tate with radiometals is simple and the radiochemical purity of prepared compounds is very high, while iodination of the peptides demands purification of the product by preparative HPLC. The analysis of rat urine showed that excretion of radioiodinated peptides included a significant proportion of metabolites.