Comparison of different methods of intracerebral administration of radioiododeoxyuridine for glioma therapy using a rat model

The Auger electron emitting agent 5-[I-125]iodo-2'-deoxyuridine (i.e. [I-12 5]IUdR) holds promise for the treatment of residual glioma after surgery be cause this thymidine analogue kills only proliferating cells. However, mali gnant cells which are not synthesizing DNA during exposure to the radiophar maceutical will be spared. To determine whether tumour incorporation of [I- 125]IUdR could be enhanced by protracted administration, we used a C6 cell line, growing in the brains of Wistar rats, as a glioma model and compared three methods of intracerebral delivery of [I-125]IUdR. Twenty-four hours a fter administration of drug, autoradiography of brain sections demonstrated nuclear uptake of the radiopharmaceutical in cells throughout tumour while normal brain cells remained free of radioactivity, The [I-125]IUdR labelli ng indices (Sb +/- s.e.m.) achieved were 6.2 (0.4) by single injection, 22. 5 (4.1) using a sustained release polymer implant (poly(lactide-co-glycolid e)) and 34.3 (2.0) by mini-osmotic pump, These results emphasize the need f or a sustained delivery system as a prerequisite for effective treatment. T hese findings are also encouraging for the development of a sustained relea se system for radiolabelled IUdR for use in the treatment of intracranial t umours, particularly in the immediate postoperative setting. (C) 2000 Cance r Research campaign.