Dynamic SIMS ion microscopy imaging of intracellular boron accumulation from carboranyl nucleosides in glioma cells.
BACKGROUND
Selective accumulation of boron-10 isotope in the nuclei of cancer cells is pivotal to the success of Boron Neutron Capture Therapy (BNCT). Sophisticated microanalytical techniques are needed for checking the selectivity and boron delivery characteristics of experimental BNCT drugs. The present study employs a secondary ion mass spectrometry (SIMS) based subcellular isotopic imaging technique of ion microscopy for testing four carboranyl nucleosides.


METHODS
CDU, HMCDU, CTU, and CFAU were tested for their boron delivery to the nuclear and cytoplasmic compartments of U251 human and F98 rat glioma cells. Quantitative SIMS analysis of boron was carried out in cryogenically prepared cells.


RESULTS
For all drugs, the cell cytoplasm revealed significantly higher boron than the nucleus. However, the boron partitioning between the cell nucleus and the nutrient medium indicated 6.4-10.6 times higher boron in the nucleus.


CONCLUSIONS
Carboranyl nucleosides studied here may provide efficient BNCT agents and need further evaluations of their efficacy.
Gay
I
I
Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA.
Lorey
D R
DR
Schinazi
R F
RF
Morrison
G H
GH
Chandra
S
S
D000818:Animals; D001896:Boron Compounds / Q000493:pharmacokinetics*; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D003857:Deoxyuridine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007554:Isotopes; D008853:Microscopy / Q000379:methods; D011741:Pyrimidine Nucleosides / Q000493:pharmacokinetics*; D051381:Rats; D018629:Spectrometry, Mass, Secondary Ion / Q000379:methods*; D014407:Tumor Cells, Cultured
D001896:Boron Compounds; D007554:Isotopes; D011741:Pyrimidine Nucleosides; C087057:5-carboranyl-2'-deoxyuridine; D003857:Deoxyuridine