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Morphological Transformation of C3H 10T1/2 Cells by ^99mTc-Cardiolite

Department of Radiology, Harvard Medical School, Boston, Massachusetts

Correspondence: For correspondence or reprints contact: Amin I. Kassis, PhD, Department of Radiology, Harvard Medical School, Goldenson Bldg., 220 Longwood Ave., Boston, MA 02115-5729.

ABSTRACT

The induction of in vitro morphological transformation in C3H 10T1/2 cells by ^99mTc-Cardiolite (contents of Cardiolite kit [hexakis(2-methoxyisobutylisonitrile) and other components] plus ^99mTc generator eluate) was examined. Methods: Cells were grown for 48 h in the presence of ^99mTc-Cardiolite or decayed ^99mTc-Cardiolite (^99mTc-Cardiolite after 1 wk of storage), and cell survival and transformation were assessed by the colony-forming and focus assays, respectively. X-ray was used as a reference for radiation effects, and 20-methylcholanthrene was used as a positive control for focus formation. Results: Exposure of cells to ^99mTc-Cardiolite results in a transformation frequency that is not significantly different from that induced by the volume equivalent of decayed ^99mTc-Cardiolite. The number of foci per viable cell increases linearly from 0.17 x 10^–4 in the untreated control to 1.7 x 10^–4 at 37 kBq/mL and 30 x 10^–4 at 1100 kBq/mL ^99mTc-Cardiolite or its decayed ^99mTc-Cardiolite volume equivalent. Furthermore, exposure of cells to low extracellular concentrations of ^99mTc-Cardiolite or decayed ^99mTc-Cardiolite (cell survival, 88%) induces an 20-fold greater number of transformants per viable cell than that observed after 0.5 Gy x-irradiation, a dose that causes the same level of toxicity. Conclusion: Radioactive and decayed ^99mTc-Cardiolite induce morphological transformation of C3H 10T1/2 cells in vitro. The underlying mechanism does not seem to be related to the radiation effects of decaying ^99mTc but to chemical(s) present in the ^99mTc-Cardiolite kit.

Key Words: low-energy electrons • ^99mTc • ^99mTc-Cardiolite • ^99mTc-MIBI • neoplastic transformation