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Quantitative Imaging of a Radiotherapeutic Drug, Na₂B₁₂H₁₁SH, at Subcellular Resolution in Tissue Cultures Using Ion Microscopy¹

Department of Chemistry, Cornell University, Ithaca, New York 14853

The effectiveness of boron neutron capture therapy is predicted to be dependent not only on the amount of boron taken up by the target cells but also on the intracellular distribution of boron. Using the isotopic imaging technique ion microscopy, we have quantitatively determined uptake and intracellular distribution of Na₂B₁₂H₁₁SH, a promising boron drug for boron neutron capture therapy, in four human cell lines: U87 glioblastoma cells, HeLa epitheloid carcinoma cells, GM 2408b mutant skin fibroblasts, and GM 3348b skin fibroblasts. The boron uptake of all four cell lines, after exposure to 100–500 µg/ml Na₂B₁₂H₁₁SH, increased as the dosages were increased but showed a tendency toward saturation. Boron was more concentrated in the cytoplasm than in the nucleus but was not strongly localized within cells. There were no significant differences in boron uptake among the four cell lines. A retention experiment identified at least two different intracellular boron pools, and cells lost >60% of intracellular boron within 1 h upon changing to Na₂B₁₂H₁₁SH-free medium, indicating a largely low affinity binding.

¹ Supported by United States Department of Energy Grant DE-FG02-91ER61138 and NIH Grant GM 24314 to G. H. M.; W. A. A. was partially supported by the Department of Energy-funded Power Burst Facility/Boron Neutron Capture Therapy Program for Cancer Research.

² Current address: SRI International, 333 Ravenswood Ave., Menlo Park, CA 94025.

³ To whom requests for reprints should be addressed, at Baker Laboratory of Chemistry, Cornell University, Ithaca, NY 14853.

Received 2/17/92. Accepted 7/23/92.

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