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INTRODUCTION (131)I-meta iodobenzylguanidine ((131)I-mIBG) therapy is established palliation for relapsed neuroblastoma. The topoisomerase-1 inhibitor, topotecan, has direct activity against neuroblastoma and acts as a radiation sensitiser. These 2 treatments are synergistic in laboratory studies. Theoretically, the benefit of (131)I-mIBG treatment could be(More)
UNLABELLED Iodine-131-metaiodobenzylguanidine ([131I]MIBG) is a radiopharmaceutical for imaging as well as targeted radiotherapy of neuroblastoma. It is predicted that the use of no-carrier-added [131I]MIBG, rather than the conventional low specific activity preparation, will result in an enhanced therapeutic ratio because of different transport processes(More)
Mathematical models have predicted that targeted radiotherapy of neuroblastoma with metaiodobenzylguanidine (mIBG) is less likely to cure small rather than large micrometastases if 131I is the conjugated radionuclide. This study uses multicellular tumour spheroids as an in vitro model to test the hypothesis that smaller tumours of sub-millimetre dimensions(More)
BACKGROUND The radiopharmaceutical 131I-metaiodobenzylguanidine (131I-MIBG) is used for the targeted radiotherapy of noradrenaline transporter (NAT)-expressing neuroblastoma. Enhancement of 131I-MIBG's efficacy is achieved by combination with the topoisomerase I inhibitor topotecan - currently being evaluated clinically. Proteasome activity affords(More)
MIBG is selectively concentrated in neuroblastoma cells, and radioiodinated MIBG has been used with some success for targeted radiotherapy. However, long-term cure remains elusive, and the topoisomerase I inhibitor topotecan may improve upon existing [131I]MIBG therapy. While synergistic killing by combinations of ionising radiation and topoisomerase I(More)
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(More)
Both electron spectroscopic imaging (ESI) and electron energy-loss spectroscopy (EELS) have great potential for use in several areas of cancer research. In biologically targeted radiotherapy, cytotoxic drug therapy and boron neutron capture therapy the effectiveness of many drugs is often critically dependent upon the intracellular localization of the agent(More)
Metaiodobenzylguanidine (MIBG) is an enzymatically stable synthetic analog of norepinephrine that when radiolabled with diagnostic ((123)I) or therapeutic ((131)I) isotopes has been shown to concentrate highly in sympathetically innervated tissues such as the heart and neuroendocrine tumors that possesses high levels of norepinephrine transporter (NET). As(More)
In vitro and in vivo neuroblastoma models were used to determine whether improvements in tumour targeting in vivo and therapeutic efficacy in vitro could result from the use of no-carrier-added (n.c.a.) [131I]MIBG. Results were compared with use of the conventional therapy MIBG preparation (ex. [131I]MIBG) of lower specific activity which is produced by(More)
UNLABELLED Recent studies have shown that indirect effects of ionizing radiation may contribute significantly to the effectiveness of radiotherapy by sterilizing malignant cells that are not directly hit by the radiation. However, there have been few investigations of the importance of indirect effects in targeted radionuclide treatment. Our purpose was to(More)