Treatment of transplanted tumor of lung adenocarcinoma A549 transfected by human somatostatin receptor subtype 2 (hsstr2) gene with 188Re-RC-160

Zhao, Rong; Yang, Weidong; Wang, Zhe; Li, Guoquan; Qin, Weiwei; Wang, Jing

doi:10.1016/j.nucmedbio.2010.05.007

« Previous Next »Nuclear Medicine and Biology
Volume 37, Issue 8 , Pages 977-987, November 2010

Treatment of transplanted tumor of lung adenocarcinoma A549 transfected by human somatostatin receptor subtype 2 (hsstr2) gene with ¹⁸⁸Re-RC-160

Rong Zhao
- Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China
Weidong Yang
- Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China
Zhe Wang
- Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China
Guoquan Li
- Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China
Weiwei Qin
- Laboratory of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, Shaanxi 710032, China
Jing Wang
- Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China
- Corresponding author. Tel.: +86 029 84775449; fax: +86 029 81230242.

Received 11 April 2010; received in revised form 18 May 2010; accepted 21 May 2010. published online 26 July 2010.

Abstract

Background and aim

Radionuclide-labeled somatostatin analogues selectively target somatostatin receptor (SSTR)-expressing tumors as a basis for diagnosis and treatment of these tumors. To those tumors without somatostatin receptor expressed, the hSSTR2 gene was transfected. Express of the hSSTR2 receptor was imaging and the radiotherapeutic effect was evaluated with ¹⁸⁸Re-RC-160.

Methods

The stable hSSTR2-expressing A549 cells (pcDNA3-hSSTR2 A549) and non-somatostatin receptor expressing A549 cells (pcDNA3 A549) were selected by western blot. Later, a corresponding animal tumor model was established. Expression of the hSSTR2 reporter was imaged using ¹⁸⁸Re-RC-160 recognition. Tumors were evaluated for somatostatin receptor expression using immunohistochemistry. The distribution of ¹⁸⁸Re-RC-160 in the animal tumor model was measured and the inhibitory effects of ¹⁸⁸Re-RC-160 were evaluated by measurement of tumor growth and hematoxylin and eosin and TdT mediated dUTP nick end labeling (TUNEL) staining.

Results

In vivo radioimaging revealed specific targeting of ¹⁸⁸Re-RC-160 to tumors derived from pcDNA3- hSSTR2 A549 cells, compared to those from pcDNA3 A549 cells. pcDNA3- hSSTR2 A549 tumor growth inhibition was significantly higher in the single 7.4 MBq ¹⁸⁸Re-RC-160 treatment group than in the 2×7.4 MBq rhenium-188, RC-160 group, control group, and pcDNA3 A549 tumors (P<.05). Furthermore, treatment fractionation group (2×7.4 MBq ¹⁸⁸Re-RC-160), induced significantly increased tumor-growth inhibition compare with single 7.4 MBq ¹⁸⁸Re-RC-160 treatment (P<.05).

Conclusion

These studies showed that ¹⁸⁸Re-RC-160 could be effectively used for targeting therapy the A549-derived tumors exogenously expressing hSSTR2, which will offers a potential therapeutic strategy for the treatment of somatostatin receptor-negative cancers.

Keywords: hSSTR2, ¹⁸⁸Re-RC-160, A549, pcDNA3-hSSTR2 A549, pcDNA3 A549, Targeting therapy