Abstract
MANY of the physical and biological requirements for treating cancer with internally emitting radionuclides are met by 5-125I-iododeoxyuridine (125IUdR). The decay of 123I is associated with a highly localised deposition of energy1. Cascades of very low energy and thus densely ionising Auger electrons are released. In addition, a charge transfer reaction takes place leaving the resultant tellurium nucleus with a transient mean net charge of +9 (ref. 2). These unique physical characteristics can be used for cell destruction by labelling DNA with 125IUdR, a thymidine analogue. The marked radiotoxicity of 125I incorporated into DNA as 125IUdR has been demonstrated by lethality, mutations and DNA strand breaks in bacteria and bacteriophage3–7, by lethality and chromosome aberrations in mammalian cells cultured in vitro8–10, and by diminished survival of prelabelled tumour cells assayed in vivo11. The intranuclear location is of major importance: 125I located extracellularly9 or bound to cell membranes is much less toxic (unpublished work of R. L. Warters and K. G. Hofer). These findings suggested that 125IUdR might have significant anti-neoplastic activity. We tested this hypothesis in a murine ascites tumour model12,13. In a pilot study using therapeutic doses of 125IUdR, the agent substantially augmented the median and absolute survival of treated animals. The critical factors affecting treatment of a 1-d-old ascites tumour model with 125IUdR are detailed here.
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