Applications of Gene Transfer to Targeted Radiotherapy

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 [131I]iodide treatment of disseminated thyroid carcinoma. The radiopharmaceutical [131I]meta-iodobenzylguanidine ([131I]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.

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

“…For example, it has been shown that the treatment of tumor cells with a variety of metabolic effectors resulted in increased accumulation of subsequently given [ 131 I]MIBG (19,20). Conversely, cell kill resulting from cytotoxic drug treatments could also reduce the capacity of tumors to actively concentrate [ 131 I]MIBG with subsequent decrease in the magnitude of the radiation cross-fire component of cell kill (21).…”

Combining a targeted radiotherapy and gene therapy approach for adenocarcinoma of prostate

“…Previously, we have demonstrated that plasmid-mediated transfection of the NAT gene into glioma cells, which do not endogenously possess NAT, leads to expression of a functional transporter, demonstrating the potential application of [ 131 I]MIBG therapy for malignancies other than neuroendocrine tumours. [8][9][10] One means of limiting the expression of the NAT transgene to tumour cells is by placing the transgene under the control of a tumour-specific promoter, such as telomerase. 11,12 This is an especially attractive component of gene therapy of prostate cancer since there is increased expression of both the RNA component, human telomerase RNA (hTR), and the protein component, human telomerase reverse transcriptase (hTERT) in cancer cells, including prostate cancer, with little expression in normal cells.…”