Intracerebral delivery of 5-iodo-2′-deoxyuridine in combination with synchrotron stereotactic radiation for the therapy of the F98 glioma

Abstract

Iodine-enhanced synchrotron stereotactic radiotherapy takes advantage of the radiation dose-enhancement produced by high-Z elements when irradiated with mono-energetic beams of synchrotron X-rays. In this study it has been investigated whether therapeutic efficacy could be improved using a thymidine analogue, 5-iodo-2'-deoxyuridine (IUdR), as a radiosentizing agent. IUdR was administered intracerebrally over six days to F98 glioma-bearing rats using Alzet osmotic pumps, beginning seven days after tumor implantation. On the 14th day, a single 15 Gy dose of 50 keV synchrotron X-rays was delivered to the brain. Animals were followed until the time of death and the primary endpoints of this study were the mean and median survival times. The median survival times for irradiation alone, chemotherapy alone or their combination were 44, 32 and 46 days, respectively, compared with 24 days for untreated controls. Each treatment alone significantly increased the rats' survival in comparison with the untreated group. Their combination did not, however, significantly improve survival compared with that of X-irradiation alone or chemotherapy alone. Further studies are required to understand why the combination of chemoradiotherapy was no more effective than X-irradiation alone.

Dependence of Cell Survival on Iododeoxyuridine Concentration in 35-keV Photon-Activated Auger Electron Radiotherapy

“…Harrington et al (9) showed improvement in time to volume tripling of KB xenographs in mice receiving five fractions at 3 Gy/fraction using pegylated liposomal IUdR (PLIUdR) + 137 Cs gamma rays (34 days), as compared to PLIUdR (9 days) or 137 Cs gamma rays (19 days) alone. By contrast, Rousseau et al (10) showed no significant difference in median survival of rats with F98 glioma that received 15 Gy in one fraction when using IUdR + 50 keV photons (46 days) and 50 keV photons alone (44 days). More recently, combinations of conventional radiation with the less toxic prodrug 5-iodo-2-pyrimidinone-2'-deoxyribose (IPdR) have been found to significantly inhibit growth of human colorectal and glioblastoma xenografts, over the inhibition due to radiation alone (6,11).…”

“…As confidence intervals for the data were needed, all data points were included in the non-weighted analysis. The SER 10 values were calculated, and standard errors (1s) for SER 10 values computed by propagating errors in D 10 , dose for 10% SF. Standard errors in D 10 were estimated as one half of the dose range spanned by the 95% confidence interval (2s) for the LQ fits to the measured data.…”

Gold Nanoparticle Imaging and Radiotherapy of Brain Tumors in Mice

“…injection of iodine contrast medium, which demonstrated the method to be safe and potentially beneficial [15]. Monochromatic synchrotron x-rays are currently being considered for iodine-enhanced treatment of brain tumors [16–18]. However, the difficulty with the low-molecular-weight iodine agents involves achieving a high enough concentration in tumors [16].…”

Nanomedicine to overcome radioresistance in glioblastoma stem-like cells and surviving clones

“…Recently, Rousseau and coworkers used 5-iodo-2 0 -deoxyuridine (IUdR) as a radiosensitizer in a F98 glioma-bearing rat model and in association with synchrotron X-rays. Although treated rats survived longer in comparison with the untreated group, the combination of treatments did not significantly improve survival compared with X-irradiation or chemotherapy alone [151]. Hence, the development of iodine microspheres or nanoparticles may be useful in that context [152] (Table 2).…”