生长抑素类似物EDDA/HYNIC-Lys0-TOCA的99Tcm标记及动物实验

本文设计合成了新的生长抑素类似物99Tcm-EDDA/HYNIC-Lys0-TOCA，并进行了正常小鼠及荷瘤裸鼠体内分布和显像，以探讨99Tcm-EDDA/HYNIC-Lys0-TOCA作为生长抑素受体阳性肿瘤显像药物的可能性。合成了Nε-HYNIC-Lys0-TOCA及其中间产物，并经核磁共振谱和质谱等分析确证。在优化的标记条件下，99Tcm-EDDA/HYNIC-Lys0-TOCA的标记率为96%左右，经Sep-Pak柱纯化后，放化纯达99%以上。体外稳定性实验及小鼠尿样分析表明标记物具有很好的体内外稳定性。99Tcm-EDDA/HYNIC-Lys0-TOCA在正常小鼠体内的清除非常迅速(血液半衰期为20min左右)，主要通过肾脏途径代谢，同时在胃、肺和肾上腺也有相对较高的放射性摄取。荷瘤裸鼠体内分布实验显示该药物在肿瘤组织有较高的放射性摄取，给药1h后肿瘤与血、肌肉等组织有较高的T/NT比值。γ显像表明，在给药后1h至2h，肿瘤组织有明显的放射性摄取，显像清晰。初步研究结果显示，该药物有望发展成为生长抑素受体阳性肿瘤的显像剂。

Preparation and Imaging Studies of 99Tcm-EDDA/HYNIC-Lys0-TOCA

The new somatostatin analogue 99Tcm-EDDA/HYNIC-Lys0-TOCA was designed and synthesized. The biological studies were carried out in normal and tumor-bearing nude mice in order to evaluate its potential application as an imaging agent for somatostatin receptor positive tumor. The labelling efficiency of 99Tcm-EDDA/HYNIC-Lys0-TOCA was approximately 96% under the optimized conditions, and more than 99% could be reached after Sep-pak column purification. The radiolabelled complex showed satisfactory stability in vitro . 99Tcm-EDDA/HYNIC-Lys0-TOCA displayed a rapid blood clearance ( about 20min of half-life) and the predominant excretion via the kidney and urinary system in normal mice. Meanwhile, the substantial uptakes of radioactivity in stomach, lung and adrenal were observed. The biodistribution in tumor-bearing nude mice of 99Tcm-EDDA/HYNIC-Lys0-TOCA suggested that there was high radioactivity uptake in tumor and rapid blood clearance, and thus high T/NT ratios of tumor to blood and muscle were obtained 1h post injection. The radio-tracer remained almost stable in urine as assayed by HPLC. Planar gamma imaging allowed contrasting visualisation of tumours at 1h and 2h post injection. All these results indicated that 99Tcm-EDDA/HYNIC-Lys0-TOCA is a novel promising candidate for somatostatin receptor -positive tumor imaging.