Monitoring of gene transfer for cancer therapy with radioactive isotopes

Gene therapy for cancer has recently been developed, and four approaches are currently being evaluated in experimental and clinical studies: 1) protection of normal tissue, such as bone marrow, which are normally targets for cytotoxic drugs; 2) improvement of the host antitumor response by increasing the antitumor activity of tumor-infiltrating immuno-competent cells or by modifying the tumor cells to enhance their immunogenicity; 3) reversion of the malignant phenotype either by suppression of oncogene expression or by introduction of normal tumor suppressor genes; 4) direct killing of tumor cells by the transfer of cytotoxic or prodrug-activating genes. Monitoring of gene therapy by assessing metabolic effects or the uptake of a specific substance with radioactive isotopes is reviewed. The author's experience is mostly described: uptake measurements with 11 Cthymidine, 18FDG, 3-D-methylglucose, and methionine in the presence of different concentrations of ganciclovir after transfection of a rat hepatoma cell line with a retroviral vector containing the HSVtk gene. Non-suicide reporter gene approaches are also discussed. (K.H.)