Slooter G D, Breeman W A, Marquet R L, Krenning E P, van Eijck C H
Department of Surgery, University Hospital, Rotterdam, The Netherlands.
Int J Cancer. 1999 May 31;81(5):767-71. doi: 10.1002/(sici)1097-0215(19990531)81:5<767::aid-ijc17>3.0.co;2-t.
Most neuroendocrine tumours and several other tumours, such as breast carcinoma and malignant lymphoma, express somatostatin receptors (SS-Rs). Lesions expressing these receptors can be visualised by receptor scintigraphy using a low radioactive dose of the radiolabelled SS analogue [111In-DTPA0]octreotide. This radioligand is internalised and transported to the lysosomes with a long residence time of 111In. The aim of this experimental study in rats was to investigate whether the same agent, given in a high radioactive dose, can be used for therapy of hepatic metastases of different tumour cell lines. The development of hepatic metastases was determined 21 days after direct injection of SS-R-positive or -negative tumour cells into the vena porta in rats. On day 1 and/or 8, animals were treated with 370 MBq (0.5 microg) [111In-DTPA0]octreotide. In one experiment, using SS-R-positive tumour cells, animals were pre-treated with a high dose of cold octreotide to block the SS-R by saturation. The number of SS-R-positive liver metastases was significantly decreased after treatment with [111In-DTPA0]octreotide. Blocking the SS-R by octreotide substantially decreased the efficacy of treatment with [111In-DTPA0]octreotide, suggesting that the presence of SS-R is mandatory. This was confirmed by the finding that the number of SS-R-negative liver metastases was not affected by treatment with [111In-DTPA0]octreotide. Therefore, we conclude that (i) high radioactive doses of [111In-DTPA0]octreotide for PRRT (peptide receptor radionuclide therapy) can inhibit the growth of SS-R-positive liver metastases in an animal model, (ii) PRRT is effective only if SS-Rs are present on the tumours, (iii) the effect of PRRT with [111In-DTPA0]octreotide can be reduced by pre-treatment with cold octreotide, which indicates that receptor binding is essential for PRRT. Our data suggest that PRRT with radiolabelled octreotide might be a new promising treatment modality for SS-R-positive tumours.
大多数神经内分泌肿瘤以及其他一些肿瘤，如乳腺癌和恶性淋巴瘤，均表达生长抑素受体（SS-Rs）。使用低放射性剂量的放射性标记SS类似物[111In-DTPA0]奥曲肽，通过受体闪烁显像可使表达这些受体的病变显影。这种放射性配体被内化并转运至溶酶体，111In在其中停留时间较长。本大鼠实验研究的目的是探究给予高放射性剂量的同一药物是否可用于治疗不同肿瘤细胞系的肝转移灶。在大鼠门静脉直接注射SS-R阳性或阴性肿瘤细胞21天后，确定肝转移灶的形成情况。在第1天和/或第8天，用370 MBq（0.5 μg）的[111In-DTPA0]奥曲肽对动物进行治疗。在一项实验中，使用SS-R阳性肿瘤细胞，先用高剂量的冷奥曲肽对动物进行预处理以通过饱和作用阻断SS-R。用[111In-DTPA0]奥曲肽治疗后，SS-R阳性肝转移灶的数量显著减少。奥曲肽阻断SS-R可显著降低[111In-DTPA0]奥曲肽的治疗效果，这表明SS-R的存在是必需的。这一发现得到了证实，即[111In-DTPA0]奥曲肽治疗对SS-R阴性肝转移灶的数量没有影响。因此，我们得出结论：（i）用于肽受体放射性核素治疗（PRRT）的高放射性剂量的[111In-DTPA0]奥曲肽可在动物模型中抑制SS-R阳性肝转移灶的生长；（ii）只有肿瘤上存在SS-R时，PRRT才有效；（iii）冷奥曲肽预处理可降低[111In-DTPA0]奥曲肽PRRT的效果，这表明受体结合对PRRT至关重要。我们的数据表明，放射性标记奥曲肽的PRRT可能是一种治疗SS-R阳性肿瘤的新的有前景的治疗方式。
