Applications of Gene Transfer to Targeted Radiotherapy

R.   J.   Mairs; S.   H.   Cunningham; M.      Boyd; S.      Carlin

Abstract

For targeted radionuclide therapy to succeed as a single modality treatment, schemes must be devised which will enable the deposition in malignant cells of sterilising doses of radiation. Until such methods have been perfected, it is necessary to combine targeted radiotherapy in a rational manner with conventional anti-cancer treatments. Several means of delivery of therapeutic radionuclides are being evaluated but none of these yet appears to be as powerful as the simplest and most effective example, viz sodium ( 131 I)iodide treatment of disseminated thyroid carcinoma. The radiopharmaceutical ( 131 I)meta-iodobenzylguanidine ( 131 I MIBG) is an effective single agent for the treatment of neuroblastoma. However, uptake of the drug in malignant sites is heterogeneous, suggesting that this therapy alone is unlikely to cure disease. A growing body of experimental evidence indicates exciting possibilities for the integration of gene transfer with radionuclide targeting. This review covers aspects of the combination of gene manipulation and targeted radiotherapy, emphasising the potential of gene transfer to facilitate tumour targeting with low molecular weight radiopharmaceuticals.

Keywords: Gene Transfer, Targeted Radiotherapy, Neuroblastoma, Cytotoxic radionuclides, Antigen Gene Expression, Antibody Targeting, Carcinoembryonic antigen, Radiolabelled, Tumours, Anti mouse immunoglobulin responses, Receptor gene expression, Peptide Targeting, Sodium iodide symporter gene transfection, Tumour cells, Noradrenaline transporter, UVW NIS, UVW GFP, Untransfected UVW spheroids, Mosaic spheroid, NAT transfectants, GFP transfected, MIBG interactions, Sequencing, Radiological bystander effect