Use of the rat pancreatic CA20948 cell line for the comparison of radiolabelled peptides for receptor-targeted scintigraphy and radionuclide therapy

Use of the rat pancreatic CA20948 cell line for the comparison of radiolabelled peptides for receptor-targeted scintigraphy and radionuclide therapy
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DOI:
10.1097/00006231-200011000-00015
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发表时间:
2000-11-01
影响因子:
1.5
通讯作者:
De Jong, M
De Jong, M
中科院分区:
医学4区
文献类型:
--
作者:
Bernard, BF;Krenning, E;De Jong, M

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我们评估了大鼠胰腺 CA20948 肿瘤作为体外细胞培养模型和 Lewis 大鼠体内模型的有用性,比较了不同的放射性标记肽用于受体靶向闪烁扫描。在体外,证明了生长抑素、铃蟾肽、P物质和胆囊收缩素的不同放射性标记类似物的受体特异性摄取和内化。根据与其各自受体的高亲和力结合来选择类似物。将它们在 CA20948 细胞中的摄取和内化与 AR42J 细胞中的这些过程进行比较,AR42J 细胞是一种用于肽受体研究的著名大鼠胰腺肿瘤细胞系。在所有测试的肽类似物的 CA20948 和 AR42J 细胞中都发现了受体特异性内化,该内化被过量的未标记肽类似物阻断。这表明所有不同肽都有特定的受体表达,使这些细胞非常适合肽研究。不同肽的内化按升序排列如下:[In-111-DOTA(0)]CCK [In-111-DOTA(0)]CCK,这与体外研究结果不同,表明肿瘤细胞上不同肽受体在体外和体内的受体数量不同,或者肽之间在代谢稳定性方面的差异。可以得出结论,CA20948肿瘤,无论是在细胞培养物中还是在大鼠中作为实体瘤,对于肽受体闪烁扫描和放射性核素治疗研究都是非常有用的模型。 ((C) 2000 Lippincott Williams & Wilkins)。
We have evaluated the usefulness of the rat pancreatic CA20948 tumour as an in vitro cell culture model and as an in vivo model in Lewis rats comparing different radiolabelled peptides for receptor-targeted scintigraphy. In vitro the receptor-specific uptake and internalization of different radiolabelled analogues of somatostatin, bombesin, substance P and cholecystokinin were demonstrated. Analogues were selected based on high-affinity binding to their respective receptors. Their uptake and internalization in CA20948 cells were compared to these processes in AR42J cells, a well-known rat pancreatic tumour cell line used for peptide-receptor studies. Receptor-specific internalization, which was blocked by excess unlabelled peptide analogue, was found in both the CA20948 and AR42J cells for all the peptide analogues tested. This indicates specific receptor expression for all the different peptides, making these cells highly suitable for peptide studies. Internalization of the different peptides was as follows, in increasing order: [In-111-DOTA(0)]CCK [In-111-DOTA(0)]CCK, which is different from the in vitro findings and points to Either different receptor numbers on the tumour cells for the different peptide receptors in vitro and in vivo or to differences between the peptides with regard to metabolic stability. It can be concluded that the CA20948 tumour, both in cell culture and as a solid tumour in rats, is a very useful model for peptide receptor scintigraphy and radionuclide therapy studies. ((C) 2000 Lippincott Williams & Wilkins).