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

A. McCluskey, Marie Boyd, S.L. Pimlott, J.W. Babich, M.N. Gaze, R.J. Mairs

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.
LanguageEnglish
PagesS28-S35
JournalBritish Journal of Radiology
Volume81
Issue numberS1
DOIs
Publication statusPublished - 2008

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3-Iodobenzylguanidine
Topotecan
Neuroblastoma
Norepinephrine Plasma Membrane Transport Proteins
Appointments and Schedules
DNA Damage
Topoisomerase I Inhibitors
Comet Assay
Radiopharmaceuticals
DNA Fragmentation
Transgenes
Heterografts
Nude Mice
Glioma
DNA Repair
Neoplasms
Cell Cycle
Flow Cytometry

Keywords

  • noradrenaline transporter
  • beta-lapachone
  • damage repair
  • camptothecin
  • inhibitors
  • therapy

Cite this

McCluskey, A. ; Boyd, Marie ; Pimlott, S.L. ; Babich, J.W. ; Gaze, M.N. ; Mairs, R.J. / Experimental treatment of neuroblastoma using [131I]meta-iodobenzylguanidine and topotecan in combination. In: British Journal of Radiology. 2008 ; Vol. 81, No. S1. pp. S28-S35.
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Experimental treatment of neuroblastoma using [131I]meta-iodobenzylguanidine and topotecan in combination. / McCluskey, A.; Boyd, Marie; Pimlott, S.L.; Babich, J.W.; Gaze, M.N.; Mairs, R.J.

In: British Journal of Radiology, Vol. 81, No. S1, 2008, p. S28-S35.

Research output: Contribution to journalArticle

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