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The Strathprints institutional repository is a digital archive of University of Strathclyde research outputs. Strathprints provides access to thousands of Open Access research papers by University of Strathclyde researchers, including those from the School of Psychological Sciences & Health - but also papers by researchers based within the Faculties of Science, Engineering, Humanities & Social Sciences, and from the Strathclyde Business School.

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Experimental treatment of neuroblastoma using [131I]meta-iodobenzylguanidine and topotecan in combination

McCluskey, A. and Boyd, Marie and Pimlott, S.L. and Babich, J.W. and Gaze, M.N. and Mairs, R.J. (2008) Experimental treatment of neuroblastoma using [131I]meta-iodobenzylguanidine and topotecan in combination. British Journal of Radiology, 81 (S1). S28-S35. ISSN 0007-1285

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Abstract

The radiopharmaceutical [I-131]meta-iodobenzylguanidine ([I-131]MIBG) and the topoisomerase I inhibitor topotecan are both effective as single-agent treatments of neuroblastoma. Our purpose was to assess the therapeutic potential of [I-131]MIBG and topotecan in combination using SK-N-BE(2c) neuroblastoma cells and UVW/NAT glioma cells expressing the noradrenaline transporter transgene. Topotecan treatment was given (i) before, (ii) after or (iii) simultaneously with [I-131]MIBG. DNA fragmentation was evaluated by comet assay and cell cycle redistribution was determined by fluorescence-activated cell sorting. Combination index analysis indicated that delivery schedules (ii) and (iii) were more effective than schedule (i) with respect to clonogenic cell kill. Similarly, significant DNA damage was observed following treatment schedules (ii) and (iii) (p <0.005), but not (i). Prior exposure to topotecan did not significantly enhance [I-131]MIBG uptake in athymic mice bearing tumour xenografts. We conclude that the enhancement of the efficacy of [I-131]MIBG by combining it with topotecan was the result of inhibition of DNA damage repair rather than an increase in expression of the noradrenaline transporter by tumour.