Development of 111In labeled insulin for receptor imaging/therapy
Development of 111In labeled insulin for receptor imaging/therapy
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DOI：
10.1007/s10967-008-7360-y
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发表时间：
2009-03-01
影响因子：
1.6
通讯作者：
Rowshanfarzad, P.
中科院分区：
文献类型：
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作者：
Jalilian, A. R.;Garousi, J.;Rowshanfarzad, P.
为了在各种糖尿病和胰岛素瘤条件下靶向胰岛素受体，在与新鲜制备的环状 DTPA-二酐 (ccDTPA) 缀合后，人重组胰岛素连续被 [In-111]-氯化铟标记。通过将 0.5 mL 胰岛素药物溶液（5 mg/mL，在磷酸盐缓冲液中，pH 8）添加到预涂有 DTPA-二酐（0.01 mg）的玻璃管中，在 25 A 摄氏度下连续温和搅拌 30 分钟，获得最佳结合结果。放射薄层色谱 (RTLC)、即时薄层色谱 (ITLC) 和高效液相色谱 (HPLC) 在优化条件下显示总体放射化学纯度高于 93%（比活度 = 550-750 MBq/mg，放射化学产率 = 81%）。示踪剂的白细胞标记能力在 37°C 下测定长达 4 小时。在正常大鼠模型中进行初步体内研究以确定放射性示踪剂的生物分布长达 48 小时。它显示示踪剂的肝脏和脾脏摄取量较高，这与其他报道的放射性标记胰岛素一致。 SPECT 图像还显示示踪剂在肝脏中大量积累。
In order to target insulin receptors in various diabetic and insulinoma conditions, human recombinant insulin was successively labeled with [In-111]-indium chloride after conjugation with freshly prepared cyclic DTPA-dianhydride (ccDTPA). The best results of the conjugation were obtained by addition of 0.5 mL of an insulin pharmaceutical solution (5 mg/mL, in phosphate buffer, pH 8) to a glass tube pre-coated with DTPA-dianhydride (0.01 mg) at 25 A degrees C with continuous mild stirring for 30 minutes. Radio-thin layer chromatography (RTLC), instant thin layer chromatography (ITLC) and high performance liquid chromatography (HPLC) have shown an overall radiochemical purity of higher than 93% at optimized conditions (specific activity = 550-750 MBq/mg, radiochemical yield =81%). The white blood cell labeling capacity of the tracer was determined up to 4 hours at 37 A degrees C. Preliminary in vivo studies in normal rat model was performed to determine the biodistribution of the radiotracer up to 48 hours. It showed a high liver and spleen uptake of the tracer which is consistent with other reported radiolabeled insulins. SPECT images have also shown high liver accumulation of the tracer.