Comparison of different methods of intracerebral administration of radioiododeoxyuridine for glioma therapy using a rat model.
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.
Mairs
R J
RJ
Department of Radiation Oncology, University of Glasgow, CRC Beatson Laboratories, UK.
Wideman
C L
CL
Angerson
W J
WJ
Whateley
T L
TL
Reza
M S
MS
Reeves
J R
JR
Robertson
L M
LM
Neshasteh-Riz
A
A
Rampling
R
R
Owens
J
J
Allan
D
D
Graham
D I
DI
D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D020099:Coated Materials, Biocompatible / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D005910:Glioma / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D007065:Idoxuridine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007457:Iodine Radioisotopes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019344:Lactic Acid / Q000008:administration & dosage*; D008297:Male; D011100:Polyglycolic Acid / Q000008:administration & dosage*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage*; D019275:Radiopharmaceuticals / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
D020099:Coated Materials, Biocompatible; D007457:Iodine Radioisotopes; D011108:Polymers; D019275:Radiopharmaceuticals; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D007065:Idoxuridine