Study of Apoptosis Induced by 188 Re-DTPA-DG in MCF-7 Breast Carcinoma and A549 Pulmonary Carcinoma Cells

Objective: To evaluate apoptosis induced by rehenium-188-labeled diethylenetriamine pentaacetic acid-glucosamine (¹⁸⁸Re-DTPA-DG) in MCF-7 breast carcinoma cells and A549 pulmonary carcinoma cells. Methods: Through the use of flow cytometry (FCM) with CBA software to detect apoptosis, cells of both the MCF-7 and A549 cell lines were divided into groups exposed to ¹⁸⁸Re-DTPA-DG, ¹⁸⁸Re-perrhenate (¹⁸⁸ReO⁻ ₄), and saline, respectively. The first two groups were further divided into subgroups on the basis of their exposure to radioactivity at 37, 55.5, or 74 kBq/mL, with the saline-exposed group divided into three corresponding subgroups. Each subgroup was introduced into 5 replicate wells of a culture plate, and the morphology of the cells in each well was determined by flow cytometry at 6-hour intervals for 18 hours. In order to determine the affinity of ¹⁸⁸Re-DTPA-DG for tumor tissue, the biodistribution of the radiolabeled agent was assessed in breast tumor-bearing nude mice. Results: Change in morphology of the cell nucleus was more evident in the ¹⁸⁸Re-DTPA-DG-treated than in the ¹⁸⁸ReO⁻ ₄-treated group, and no change in nuclear morphology was seen in the saline-exposed group. The study data suggested that there was a greater ratio of apoptotic to nonapoptotic cells among the ¹⁸⁸Re-DTPA-DG-treated than among the ¹⁸⁸ReO⁻ ₄-treated or saline-exposed cells (p < 0.01), and a greater change in cell-nuclear morphology in the ¹⁸⁸Re-DTPA-DG-treated than in the ¹⁸⁸ReO⁻ ₄-treated cells. Furthermore, ¹⁸⁸Re-DTPA-DG had a more significant apoptosis-inducing effect on both MCF-7 and A549 cells than did ¹⁸⁸ReO⁻ ₄. The biodistribution study in tumor-bearing nude mice showed that the concentration of ¹⁸⁸Re-DTPA-DG in tumor tissue was much higher than in normal tissue, that ¹⁸⁸Re-DTPA-DG was rapidly cleared from the blood, and that the main route of its clearance was via the kidneys. Conclusions: ¹⁸⁸Re-DTPA-DG has a significant apoptotic effect on carcinoma cells. ¹⁸⁸Re-DTPA-DG is an effective radiopharmaceutical for intratumoral radiation therapy.