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Cytotoxic Effects of m-[¹³¹I]- and m-[¹²⁵I]Iodobenzylguanidine on the Human Neuroblastoma Cell Lines SK-N-SH and SK-N-LO¹

Division of Hematology and Oncology, Department of Pediatrics [G. B., R. G., J. B., D. N., J. T.], Ruemelinstrasse 23 and Institute of Pathology, Liebermeisterstrasse 8 [H. W.], University of Tuebingen, D-7400 Tuebingen, West Germany

As we have reported recently, the human neuroblastoma cell line SK-N-SH is able to take up and store m-iodobenzylguanidine (mIBG). This is in contrast to several other neuroblastoma cell lines, among which are SK-N-LO cells. Both cell lines were used in cell killing experiments with unlabeled and radioactive-labeled mIBG. Using 1–200 µCi m-[¹³¹I]IBG (1 h incubation time), only SK-N-SH cells could to a large extent be destroyed in a dose-dependent manner. This effect is completely caused by the radioactive labeling of the molecule, because unlabeled mIBG proved not to be toxic in the concentration range used in experiments with radiolabeled mIBG (30 nM-3 µM). The killing effect was strongly reduced when m-[¹³¹I]IBG with low specific activity (0.2–0.3 mCi/mg) was used instead of 20–30 mCi/mg. Similar effects in both cell lines were obtained using m-[¹³¹I]- and m-[¹²⁵I]IBG. SK-N-SH cells that survived a first treatment with m-[¹³¹I]IBG were less sensitive to a second treatment. SK-N-LO cells were more sensitive against m-[¹³¹I]- and m-[¹²⁵I]IBG than SK-N-SH cells if both cell lines are exposed to these radioactive compounds over a long period of time (24 h). The reason that only SK-N-SH cells could be destroyed in short-term incubation experiments is that mIBG is stored for approximately 7 days in these cells only. SK-N-LO cells could only be destroyed to a significant degree if m-[¹³¹I]IBG was permanently present in the test system. Bone marrow stem cells (CFU-c) also proved to be sensitive against m-[¹³¹I]IBG, although the effects were less pronounced than on SK-N-SH cells.

¹ Supported by a grant from the Deutsche Krebshilfe.

² Present address: Memorial Sloan-Kettering Cancer Center, New York, NY.

³ To whom requests for reprints should be addressed.

Received 7/ 1/87. Revised 2/ 3/88. Accepted 2/26/88.