Preclinical study of radioiodinated glucose-Tyr3-octreotate:Comparison with 111In-DOTA-Tyr3-octreotate

摘要

In this study, preclinical analysis of distribution profiles and elimination pathways o ofradioiodinated glucose-Tyr3-octreotate (125I-gluc-TOCA) are presented in comparison with thatof another promising targeted radiopharmaceutical, 111In-DOTA-Tyr3-octreotate (111In-DOTATOCA).Results confirmed that specific internalization of 125I-gluc-TOCA by sstr2 – expressingAR42J rat pancreatic carcinoma cells in vitro was about twice of that for 111In-DOTA-TOCA.Radioactivity accumulation of 125I-gluc-TOCA in organs with a high density of somatostatinreceptors (pancreas and adrenals) was significantly higher and radioactivity uptake in thekidney was significantly lower in comparison with 111In-DOTA-TOCA up to 1 hr after dosing.24 and 48 hr after administration, high and long term radioactivity retention in the pancreas,adrenals and kidney was seen with 111In-DOTA-TOCA, whereas in case of 125I-gluc-TOCA asubstantial decrease in radioactivity concentrations in all organs and tissues were demonstrated.HPLC analysis of radioactivity in the urine confirmed the predominant elimination of theparent peptide with 111In-DOTA-TOCA. In case of 125I-gluc-TOCA, considerable amount of theintact peptide was found in urine 2 hr after dosing whereas 24 and 48 hr after administration,the eliminated radioactivity was mostly in the form of 125I-gluc-TOCA - metabolites. Rat liverperfusion experiments showed that bile clearance of 111In-DOTA-TOCA was very low. Insummary, 125I-gluc-TOCA exhibited higher uptake in somatostatin receptor-rich organs but itsresidence time in these organs was substantially lower when compared with 111In-DOTATOCA.