Related Experiment Video
Updated: May 12, 2026
A Practical Guide for the Production and PET/CT Imaging of 68Ga-DOTATATE for Neuroendocrine Tumors in Daily Clinical Practice
Published on: April 17, 2019
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.
Insights
This study successfully introduced human somatostatin receptors subtype-2 (hsstr2) into lung cancer cells, enabling targeted therapy with radiolabeled somatostatin analogs like (131)I-RC-160 for effective tumor inhibition.
Area of Science:
- Oncology
- Molecular Biology
- Radiopharmaceutical Therapy
Background:
- Lung carcinoma cells (A549) typically do not express somatostatin receptors.
- Somatostatin analogs, such as RC-160 (vapreotide), can target somatostatin receptors.
- Radiolabeled somatostatin analogs offer potential for targeted cancer therapy and imaging.
Purpose of the Study:
- To introduce the human somatostatin receptors subtype-2 (hsstr2) gene into A549 lung carcinoma cells.
- To investigate the role of hsstr2 in lung cancer.
- To evaluate the therapeutic efficacy of (131)I-RC-160 on hsstr2-transfected cells and tumors.
Main Methods:
- Gene transfection of A549 cells with hsstr2.
- Radioligand-receptor binding assays and internalization studies using (125)I-RC-160.
- Cell viability assays (MTT) with (131)I-RC-160, Na(131)I, and RC-160.
- In vivo tumor scintigraphy and volume measurements in nude mice xenografts using (99m)Tc-RC-160.
Main Results:
- Transfected A549-hSSTR2 cells showed significantly higher binding and internalization of radioligands compared to control cells (18.24% vs 5.7%).
- A549-hSSTR2 cells exhibited a high inhibition ratio of 78.8% when treated with (131)I-RC-160.
- Tumor scintigraphy clearly visualized lesions in nude mice, and (131)I-RC-160 significantly inhibited tumor growth in A549-hSSTR2 xenografts.
Conclusions:
- It is feasible to introduce hsstr2 into tumor cell lines lacking these receptors.
- (131)I-RC-160 demonstrates significant therapeutic potential against tumors engineered to express hsstr2.
- This approach holds promise for targeted radiopharmaceutical therapy in lung cancer.
