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 tumour-specific 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[(131)I]
MIBG was more cytotoxic than c.a.[131I]
MIBG. However, the alpha-emitter [
211At]MABG was, by three orders of magnitude, more effective in causing tumour cell kill than the beta-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.