Study of apoptosis induced by 188Re-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 (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.
Xiong
Qing-Feng
QF
Department of Nuclear Medicine, Affiliated Hospital of Luzhou Medical College, Luzhou, China.
Chen
Yue
Y
He
Ling
L
Deng
Cun-Liang
CL
Huang
Zhan-Wen
ZW
Li
Ju-Lian
JL
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009942:Organometallic Compounds / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity*; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity