Steps towards cancer therapy with radionuclides--a review including radiation biophysical aspects

Though great advantages will be connected with endoradiotherapy, a lot of problems has still to be overcome, the greatest of them being without doubt the problem of selectivity of the carrier compounds. Some few of them have proved to be able to accumulate in certain cancers by reason of their incorporation as metabolites, especially in melanomas. The other great hope are the monoclonal antibodies or their fragments, and in this field much endeavour has been spent in the last years. Especially the two-step method of loading the radioactive nuclide to the antibodies when their binding to the cancer cells is complete appears very promising. Some other, unspecific vehicles may also prove suitable for accumulation in certain tumor types. For the selection of the nuclides it has to be considered that radiation biophysical experiments demonstrated that the critical targets for radiation action are with high probability the DNA superstructure units, and that the distribution of ionizations within them is decisive for the inactivation of a cell. With sparsely ionizing radiation (e.g. beta-radiation) rather high doses are required for reaching an adequate concentration of ionizations in these DNA units. Densely ionizing radiation with an LET of about 150 keV/microns exhibits the maximum relative biological effectiveness (12-16 referred to X-radiation). Therefore emitters of alpha-particles the LET of which lies actually somewhat lower, near 100 keV/microns, seem to be very suitable for endoradiotherapy. Moreover the short ranges of these particles (about 60 microns in tissue) render an extensive sparing of the surrounding normal tissue possible. The second group of effective nuclides is that of Auger electron emitters. The low-energy proportion of Auger electrons leads to a high ionization density in small volumes. The very short ranges of these electrons (in the nanometer range), however, require an incorporation of the nuclide into the cell nucleus if an effective cell inactivation is to occur. 211At (alpha-emitter) and 125I (Auger electron emitter) already proved their high inactivating effectiveness in cell cultures and their curative action in animal experiments, and studies of binding 211At to monoclonal antibodies are encouraging. Some other approaches proposed for the transport of radionuclides into tumor cells or for generating them within tumor tissue are also aimed in essential at the release of densely ionizing alpha-particles or of Auger electrons.