Petrik Milos, Laznickova Alice, Laznicek Milan, Zalutsky Michael R
Department of Biophysics and Physical Chemistry, Faculty of Pharmacy, Charles University, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic.
Anticancer Res. 2007 Nov-Dec;27(6B):3941-6.
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.
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.
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.
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.
用放射性金属或放射性卤素标记的生长抑素类似物可用于含生长抑素受体肿瘤的成像和治疗。在本研究中，比较了葡萄糖 - 酪氨酰 -3-奥曲肽（gluc - Tyr3 - tate）的放射性碘化和用111铟、177镥和125碘对DOTA - 酪氨酰 -3-奥曲肽（DOTA - Tyr3 - tate）进行放射性标记的过程，并分析了它们在大鼠体内的代谢情况。研究了高效液相色谱（HPLC）分析和硅胶快速薄层层析（ITLC - SG）在放射性化学纯度测定和尿液代谢分析中的实用性。
对于用放射性金属进行标记，采用与肽的1,4,7,10 - 四氮杂环十二烷 -1,4,7,10 - 四乙酸（DOTA）官能团形成络合物的方法。通过氯胺 - T法进行放射性碘化。用HPLC和/或ITLC - SG方法测定放射性标记肽的放射性化学纯度和大鼠尿液分析。在消除研究中使用雄性Wistar大鼠。
DOTA - Tyr3 - tate用放射性金属简单地进行放射性标记，产率高且放射性化学纯度高。反应终止是放射性碘化的关键步骤，因此用125碘标记gluc - Tyr3 - tate和DOTA - Tyr3 - tate并不那么简单，反应产物必须通过制备型HPLC分析进行纯化。虽然111铟 - DOTA - Tyr3 - tate和177镥 - DOTA - Tyr3 - tate以几乎不变的形式从大鼠尿液中排出，但在用放射性碘标记的肽中观察到相当比例的代谢物，特别是在较长时间间隔时。
用放射性金属标记DOTA - Tyr3 - tate很简单，制备的化合物放射性化学纯度非常高，而肽的碘化需要通过制备型HPLC对产物进行纯化。大鼠尿液分析表明，放射性碘标记肽的排泄包括相当比例的代谢物。
