title: Imaging and therapy of hSSTR2-transfected tumors using radiolabeled somatostatin analogs.
abstract: The aim of this study was to introduce human somatostatin receptors subtype-2 (hsstr2) gene into A549 lung carcinoma cells in order to investigate the role of these receptors, and to observe the lethal effect of (131)I-RC-160 (RC-160, vapreotide, an analog of somatostatin) on transfected cells through tumor scintigraphy. Clones overexpressing SSTR2 were selected for radioligand-receptor binding assay and assessment of (125)I-RC-160 internalization. The methylthiazolyl tetrazolium test was used to observe the lethal effect of (131)I-RC-160, Na(131)I, and RC-160 on hSSTR2-transfected A549 cells (A549-hSSTR2). Planar imaging was performed with a gamma camera equipped with pinhole collimator in nude mice bearing both A549-hSSTR2 tumors overexpressing SSTR2 and A549-pcDNA3 (pcDNA3-transfected A549 cells) tumors as control. Images were obtained at 0.5, 6, and 24 h after injection of 3.7 × 10(6) Bq (99m)Tc-RC-160 via the tail vein. The inhibitory effects of (131)I-RC-160, RC-160, and Na(131)I on the tumors were recorded by measuring the tumor volumes. At the end of the study, the tumors were excised and HE staining was performed. The binding radioactivity (sum of membrane-bound and internalized radioligand) of A549-hSSTR2 cells was 18.24 ± 1.9 % of total counts added after 1 h of incubation, and was higher than that of A549-pcDNA3 cells 5.7 ± 1.4 % (P < 0.05). The inhibition ratio of A549-hSSTR2 cells was 78.8 ± 5.9 %. Clear images of tumor lesions in nude mice were achieved at 0.5 h post injection. In the A549-hSSTR2 xenograft tumor group, the growth of the tumors treated with (131)I-RC-160 was significantly inhibited as compared to tumors in the group treated with RC-160 (P < 0.01). This study demonstrated that it was possible to introduce hsstr2 to non-expressing tumor cell lines and treat tumors with radiolabeled somatostatin analogs.
authors.affiliation: Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.forename: Wenhui
authors.initials: W
authors.lastname: Ma
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Jinglan
authors.initials: J
authors.lastname: Deng
authors.forename: Menghui
authors.initials: M
authors.lastname: Yuan
authors.forename: Mingxuan
authors.initials: M
authors.lastname: Zhao
authors.forename: Lintao
authors.initials: L
authors.lastname: Jia
authors.forename: Weidong
authors.initials: W
authors.lastname: Yang
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Weiwei
authors.initials: W
authors.lastname: Qin
authors.forename: Dake
authors.initials: D
authors.lastname: Chu
authors.forename: Guoquan
authors.initials: G
authors.lastname: Li
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018014:Gene Transfer Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D019275:Radiopharmaceuticals; D017481:Receptors, Somatostatin / Q000235:genetics*; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D019275:Radiopharmaceuticals; D017481:Receptors, Somatostatin; C574734:SSTR2 protein, human; C051458:vapreotide; D013004:Somatostatin