Intracellular localization of metaiodobenzyl guanidine in human neuroblastoma cells by electron spectroscopic imaging

Abstract

The targeted radiotherapy of neuroblastoma with ¹³¹I-labelled metaiodobenzyl guanidine (mIBG) is now the subject of several clinical studies. The precise intracellular localization of mlBG, necessary for nuclear microdosimetry, has not previously been described. We report the use of electron-energy-loss spectroscopy and electron spectroscopic imaging to establish the intracellular distribution of mlBG in cells from the human neuroblastoma line NBI-G which had been incubated with the drug by mapping iodine in ultra-thin sections of tumours. Most of the iodine is found within the mitochondria, with lesser amounts in the vesicles and on the nuclear membrane. The use of alternative radionuclides with different physical characteristics has been suggested to optimize the efficacy of this therapeutic strategy. The lack of penetration of mIBG into the nucleoplasm means that ultra-short-range Auger electron emitters such as ¹²⁵I are not likely to prove more cytotoxic than ¹³¹I.