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

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 [177Lu-DOTAo, Tyr3]octreotate. After 21 days rats were killed and liver metastases were counted. Results: Treatment with 370 MBq [177Lu-DOTAo, 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-DOTAo, Tyr3] octreotate compared with controls. In addition, rats with mixed liver metastases treated with 185 MBq [177]Lu-DOTAo, 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 [177Lu-DOTAo, Tyr3]octreotate. This phenomenon is beneficial in the concept of in vivo gene therapy.

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