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S_inaary Radiolabelled meta-iodobenzylguanidine (mIBG) currently provides one of the most promising options for targeted radiotherapy of neuroblastoma. No means currently exists for prediction of mIBG uptake in tumour cells of individual patients other than semiquantitative inferences from diagnostic scanning which depend on the continued existence of a macroscopic tumour mass. A biological rapid assay which could be applied at initial biopsy would be invaluable in selecting patients for therapeutic strategies which incorporate radiolabeled mIBG. We have assesed the expression of the noradrenahne transporter gene in six human neuroblastoma cell lines and in three non-neural crest-derived cell lines using reverse transcription followed by the polymerase chain reaction. Transcription of this gene was observed in five out of six neuroblastoma cell lines but in none of the control cells. A highly significant correlation was established (P<0.O1) between gene expression and active cellular accumulation of mIBG. It is suggested that semiquantitative evaluation of noradrenaline transporter gene transcripts may be predictive of mIBG uptake by tumours in vivo.

The targeted radiotherapy of neuroblastoma with 131l-labelled metaiodobenzyl guanidine (mIBG) is now the subject of several clinical studies. The precise intracellular localization of mIBG, 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 mIBG 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.

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