This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by McCluskey, A. G. Articles by Mairs, R. J. Search for Related Content PubMed PubMed Citation Articles by McCluskey, A. G. Articles by Mairs, R. J.

[¹³¹I]meta-Iodobenzylguanidine and Topotecan Combination Treatment of Tumors Expressing the Noradrenaline Transporter

Authors' Affiliations: ¹ Targeted Therapy Group and Department of Child Health, University of Glasgow, Cancer Research UK Beatson Laboratories; ² Department of Surgery, University of Glasgow, Royal Infirmary, Glasgow, United Kingdom; and ³ University College London Hospitals, NHS Foundation Trust, Middlesex Hospital, London, United Kingdom

Requests for reprints: Robert J. Mairs, Department of Radiation Oncology, University of Glasgow, Cancer Research UK Beatson Laboratories, Garscube Estate, Glasgow G61 1BD, United Kingdom. Phone: 44-41-330-4126; Fax: 44-41-330-4127; E-mail: r.mairs{at}beatson.gla.ac.uk.

Purpose: Both [¹³¹I]meta-iodobenzylguanidine ([¹³¹I]MIBG) and the topoisomerase I inhibitor topotecan are effective as single-agent treatments of neuroblastoma. The aim of this study was to investigate the efficacy of [¹³¹I]MIBG in combination with topotecan in vitro and in vivo.

Experimental Design: The cell lines used were SK-N-BE(2c) (human neuroblastoma) and UVW/NAT (glioma cell line transfected with the noradrenaline transporter gene). Three different treatment schedules were assessed: topotecan given before (schedule 1), after (schedule 2), or simultaneously (schedule 3) with [¹³¹I]MIBG. DNA strand breakage was evaluated by comet assay, and cytotoxicity was determined by clonogenic survival. Efficacy was also measured by growth delay of tumor xenografts in nude mice.

Results: Combination schedules 2 and 3 caused more cytotoxicity than schedule 1. Similarly, significant DNA damage was observed following treatment schedules 2 and 3 (P < 0.005) but not schedule 1. The mean number of days for a doubling in volume of SK-N-BE(2c) tumors and a 10-fold increase in volume of UVW/NAT tumors were 10.4 and 18.6 (untreated), 19.7 and 25.3 (topotecan alone), 22.8 and 31.9 ([¹³¹I]MIBG alone), 26.3 and 37.1 (combination schedule 1), 34.3 and 49.7 (combination schedule 2), and 53.2 and >71 (combination schedule 3), respectively. The highest rate of cure of both xenografts was observed following treatment with combination schedule 3.

Conclusions: The combination of topotecan and [¹³¹I]MIBG compared with either treatment alone gave rise to greater than additive DNA damage, clonogenic cell kill, and tumor growth delay. These effects were dependent on the scheduling of the two agents.

This article has been cited by other articles:

				W. J. G. Oyen, L. Bodei, F. Giammarile, H. R. Maecke, J. Tennvall, M. Luster, and B. Brans Targeted therapy in nuclear medicine current status and future prospects Ann. Onc., November 1, 2007; 18(11): 1782 - 1792. [Abstract] [Full Text] [PDF]

				R. J. Mairs, S. C. Ross, A. G. McCluskey, and M. Boyd A Transfectant Mosaic Xenograft Model for Evaluation of Targeted Radiotherapy in Combination with Gene Therapy In Vivo J. Nucl. Med., September 1, 2007; 48(9): 1519 - 1526. [Abstract] [Full Text] [PDF]

				C. Mothersill and C. B. Seymour Targeted Radiotherapy: Is the "Holy Grail" in Sight? J. Nucl. Med., June 1, 2006; 47(6): 899 - 900. [Full Text] [PDF]