ABSTRACT
The Auger electron emitting agent 5-[125I]iodo-2'-deoxyuridine (i.e. [125I]IUdR) holds promise for the treatment of residual glioma after surgery because this thymidine analogue kills only proliferating cells. However, malignant cells which are not synthesizing DNA during exposure to the radiopharmaceutical will be spared. To determine whether tumour incorporation of [125I]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 [125I]IUdR. Twenty-four hours after 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 [125I]IUdR labelling indices (% +/- 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-glycolide)) and 34.3 (2.0) by mini-osmotic pump. These results emphasize the need for a sustained delivery system as a prerequisite for effective treatment. These findings are also encouraging for the development of a sustained release system for radiolabelled IUdR for use in the treatment of intracranial tumours, particularly in the immediate postoperative setting.
Subject(s)
Brain Neoplasms/radiotherapy , Coated Materials, Biocompatible/administration & dosage , Drug Delivery Systems/methods , Glioma/radiotherapy , Idoxuridine/administration & dosage , Iodine Radioisotopes/administration & dosage , Lactic Acid/administration & dosage , Polyglycolic Acid/administration & dosage , Polymers/administration & dosage , Radiopharmaceuticals/administration & dosage , Animals , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Female , Glioma/metabolism , Glioma/pathology , Idoxuridine/pharmacokinetics , Iodine Radioisotopes/pharmacokinetics , Male , Polylactic Acid-Polyglycolic Acid Copolymer , Radiopharmaceuticals/pharmacokinetics , Rats , Rats, Wistar , Tissue DistributionABSTRACT
The function of the compound eye is dependent upon a developmental program that specifies different cell fates and directs the expression of spectrally distinct opsins in different photoreceptor cells. Rh5 is a novel Drosophila opsin gene that encodes a biologically active visual pigment that is expressed in a subset of R8 photoreceptor cells. Rh5 expression in the R8 cell of an individual ommatidium is strictly coordinated with the expression of Rh3, in the overlying R7 cell. In sevenless mutant files, which lack R7 photoreceptor cells, the expression of the Rh5 protein in R8 cells is disrupted, providing evidence for a specific developmental signal between the R7 and R8 cells that is responsible for the paired expression of opsin genes.