Treatment of transplanted tumor of lung adenocarcinoma A549 transfected by human somatostatin receptor subtype 2 (hsstr2) gene with 188Re-RC-160.
OBJECTIVE
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 (188)Re-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 (188)Re-RC-160 recognition. Tumors were evaluated for somatostatin receptor expression using immunohistochemistry. The distribution of (188)Re-RC-160 in the animal tumor model was measured and the inhibitory effects of (188)Re-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 (188)Re-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 (188)Re-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 (188)Re-RC-160), induced significantly increased tumor-growth inhibition compare with single 7.4 MBq (188)Re-RC-160 treatment (P<.05).


CONCLUSIONS
These studies showed that (188)Re-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.
Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
Rong
R
Zhao
Weidong
W
Yang
Zhe
Z
Wang
Guoquan
G
Li
Weiwei
W
Qin
Jing
J
Wang
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D000077192:Adenocarcinoma of Lung; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D003001:Cloning, Molecular; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011868:Radioisotopes / Q000627:therapeutic use*; D017481:Receptors, Somatostatin / Q000235:genetics* / Q000378:metabolism*; D012211:Rhenium / Q000627:therapeutic use*; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use; D015899:Tomography, Emission-Computed, Single-Photon; D014162:Transfection
D011868:Radioisotopes; D017481:Receptors, Somatostatin; C051458:vapreotide; D013004:Somatostatin; D012211:Rhenium; C093733:somatostatin receptor 2