生长抑素受体基因治疗联合放射性标记奥曲肽靶向治疗：肝转移瘤的一种新疗法。

Somatostatin receptor gene therapy combined with targeted therapy with radiolabeled octreotide: a new treatment for liver metastases.

作者信息

Mearadji Amir, Breeman Wout, Hofland Leo, van Koetsveld Peter, Marquet Richard, Jeekel Johannes, Krenning Eric, van Eijck Casper

机构信息

Department of Surgery, Erasmus Medical Center Rotterdam, Rotherdam, The Netherlands.

出版信息

Ann Surg. 2002 Dec;236(6):722-8; discussion 728-9. doi: 10.1097/00000658-200212000-00004.

DOI:10.1097/00000658-200212000-00004

PMID:12454510

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1422638/

Abstract

OBJECTIVE

To evaluate the effect of peptide receptor radionuclide therapy (PRRT) on somatostatin receptor (SSR)-transfected colon carcinoma cells in a rat liver metastases model.

SUMMARY BACKGROUND DATA

Previously the authors have shown highly effective therapy with PRRT of SSR-positive tumors. This treatment is SSR-mediated; successful treatment is seen only in SSR-positive tumors, with no effect in SSR-negative tumors. As many tumors lack this receptor, the idea arose to transfect SSR-negative tumor cells with an SSR gene to apply PRRT on these SSR-transfected tumor cells.

METHODS

CC531 colon carcinoma cells (SSR-negative) were transfected in vitro with an SSR (subtype 2) gene (CC2B). Liver metastases were produced after intraportal injection of these tumor cells in rats. On day 7, animals were treated with 185 or 370 MBq [177 Lu-DOTA0, Tyr3 ]octreotate. After 21 days rats were killed and liver metastases were counted.

RESULTS

Treatment with 370 MBq [177 Lu-DOTA0, Tyr3 ]octreotate showed a significant antitumor response in rats with CC2B liver metastases (SSR-positive) in comparison with controls. No significant antitumor effect was seen in PRRT-treated rats with CC531 liver metastases (SSR-negative). Also, a dose-dependent tumor response was seen in rats with CC2B liver metastases treated with 185 MBq [ 177Lu-DOTA0, Tyr3 ]octreotate compared with controls. In addition, rats with mixed liver metastases treated with 185 MBq [177 Lu-DOTA0, Tyr3 ]octreotate had significantly fewer metastases compared with controls.

CONCLUSIONS

The authors showed an impressive antitumor effect of SSR (subtype 2)-transfected colon carcinoma cells with PRRT in a rat liver metastasis model. Moreover, rats with mixed liver metastases had significantly fewer liver metastases compared with control rats, which may be due to a radiologic bystander effect of [177 Lu-DOTA0, Tyr3 ]octreotate. This phenomenon is beneficial in the concept of in vivo gene therapy.

摘要

目的

在大鼠肝转移模型中评估肽受体放射性核素治疗（PRRT）对转染生长抑素受体（SSR）的结肠癌细胞的疗效。

总结背景数据

此前作者已证明PRRT对SSR阳性肿瘤具有高效治疗作用。这种治疗是由SSR介导的；仅在SSR阳性肿瘤中可见成功治疗效果，对SSR阴性肿瘤无效。由于许多肿瘤缺乏这种受体，因此产生了用SSR基因转染SSR阴性肿瘤细胞以对这些转染了SSR的肿瘤细胞应用PRRT的想法。

方法

将CC531结肠癌细胞（SSR阴性）在体外转染SSR（2型）基因（CC2B）。在大鼠门静脉内注射这些肿瘤细胞后产生肝转移。在第7天，用185或370MBq[177Lu-DOTA0，Tyr3]奥曲肽治疗动物。21天后处死大鼠并计数肝转移灶。

结果

与对照组相比，用370MBq[177Lu-DOTA0，Tyr3]奥曲肽治疗显示对患有CC2B肝转移（SSR阳性）的大鼠有显著的抗肿瘤反应。在用PRRT治疗的患有CC531肝转移（SSR阴性）的大鼠中未观察到显著的抗肿瘤作用。此外，与对照组相比，用185MBq[177Lu-DOTA0，Tyr3]奥曲肽治疗的患有CC2B肝转移的大鼠出现了剂量依赖性肿瘤反应。另外，用185MBq[177Lu-DOTA0，Tyr3]奥曲肽治疗的患有混合肝转移的大鼠与对照组相比转移灶明显减少。