Comparison of Radiohaloanalogues of Meta-Iodobenzylguanidine (MIBG) for a Combined Gene- and Targeted Radiotherapy Approach to Bladder Carcinoma

Fullerton, N., Boyd, M., Ross, S., Pimlott, S., Babich, J., Kirk, D., Zalutsky, M. and Mairs, R. (2005) Comparison of Radiohaloanalogues of Meta-Iodobenzylguanidine (MIBG) for a Combined Gene- and Targeted Radiotherapy Approach to Bladder Carcinoma. Medicinal Chemistry, 1(6), pp. 611-618. (doi: 10.2174/157340605774598090)

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Abstract

Targeted radiotherapy using radiolabelled meta-iodobenzylguanidine (MIBG) is a promising treatment option for bladder cancer, restricting the effects of radiotherapy to malignant cells thereby increasing efficacy and decreasing morbidity of radiotherapy. We investigated the efficacy of a combined gene therapy and targeted radiotherapy approach for bladder cancer using radiolabelled MIBG. The effectiveness of alternative radiohalogens and alternative preparations of radiolabelled MIBG for this therapeutic strategy were compared. Bladder cancer cells, EJ138, were transfected with a gene encoding the noradrenaline transporter (NAT) under the control of a tumour specific telomerase promoter, enabling them to actively take up radiolabelled MIBG. This resulted in tumourspecific cell kill. Uptake and retention of radioactivity in cells transfected with the NAT gene were compared with that obtained in cells transfected with the sodium iodide symporter (NIS) gene. Substantially greater uptake and longer retention of radioactivity in NAT-transfected cells was observed. Carrier-added (c.a.) [131I]MIBG, no-carrier added (n.c.a.) [131I]MIBG, and [211At]-labelled benzylguanidine (i.e. [211At] meta-astatobenzylguanidine (MABG)) were compared with respect to efficiency of induction of cell kill. N.c.a[131I]MIBG was more cytotoxic than c.a.[131I]MIBG. However, the agr- emitter [211At]MABG was, by three orders of magnitude, more effective in causing tumour cell kill than the bgr-emitter [131I]MIBG. We conclude that NAT gene transfer combined with the administration of n.c.a.[131I]MIBG or [211At]MABG, is a promising novel treatment approach for bladder cancer therapy.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Mairs, Professor Robert and Boyd, Dr Marie
Authors: Fullerton, N., Boyd, M., Ross, S., Pimlott, S., Babich, J., Kirk, D., Zalutsky, M., and Mairs, R.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Medicinal Chemistry
ISSN:1573-4064

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