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Study of apoptosis induced by 188Re-DTPA-DG in MCF-7 breast carcinoma and A549 pulmonary carcinoma cells.

AbstractOBJECTIVE: 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 (188ReO4-), 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 188ReO4--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 188ReO4--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 188ReO4--treated cells. Furthermore, 188Re-DTPA-DG had a more significant apoptosis-inducing effect on both MCF-7 and A549 cells than did 188ReO4-. 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.
AuthorsQing-Feng Xiong, Yue Chen, Ling He, Cun-Liang Deng, Zhan-Wen Huang, Ju-Lian Li (Affiliation: Department of Nuclear Medicine, Affiliated Hospital of Luzhou Medical College, Luzhou, China.)
JournalCancer biotherapy & radiopharmaceuticals (Cancer Biother Radiopharm) Vol. 22 Issue 4 Pg. 543-50 (Aug 2007) ISSN: 1084-9785 United States
PMID17803449 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Organometallic Compounds
  • Radiopharmaceuticals
  • Re-diethylenetriamine pentaacetic acid-glucosamine
Topics
  • Animals
  • Apoptosis (drug effects)
  • Breast Neoplasms (pathology)
  • Cell Line, Tumor
  • Humans
  • Lung Neoplasms (pathology)
  • Mice
  • Mice, Nude
  • Organometallic Compounds (chemistry, pharmacokinetics, pharmacology, toxicity)
  • Radiopharmaceuticals (chemistry, pharmacokinetics, pharmacology, toxicity)