Low Dose Rate Irradiation Research Articles

Low dose rate irradiation behaviors of Y 3+-doped PbWO 4 crystals

Light yield of some Y 3+: PWO crystals increases after irradiation, and is accompanied with transmission change in the wavelengths from 380 to 500 nm. The pre-existing 430 nm color centers or annealing induced ones are unstable during irradiation. These results interpret the temperature sensitivity of light yield and radiation hardness. A proper annealing temperature and the way to eliminate the instability are found out.

Temperature dependence of commercially available diode detectors.

Temperature dependence of commercially available n- and p-type diodes were studied experimentally under both high instantaneous dose rate (pulsed) and low dose rate (continuous) radiation. The sensitivity versus temperature was measured at SSD = 80 or 100 cm, 10 x 10 cm2, and 5 cm depth in a 30 x 30 x 30 cm3 water phantom between 10 degrees C and 35 degrees C. The response was linear for all the diode detectors. The temperature coefficient (or sensitivity variation with temperature, svwt) was dose rate independent for preirradiated diodes. They were (0.30 +/- 0.01)%/degrees C, (0.36 +/- 0.03)%/degrees C, and (0.29 +/- 0.08)%/degrees C for QED p-type, EDP p-type, and Isorad n-type diodes, respectively. The temperature coefficient for unirradiated n-type diodes was different under low dose rate [(0.16 to 0.45)%/degrees C, continuous, cobalt] and high instantaneous dose rate [(0.07 +/- 0.02)%/degrees C, pulsed radiation]. Moreover, the temperature coefficient varies among individual diodes. Similarly, the temperature coefficient for a special unirradiated QED p-type diode was different under low dose rate (0.34%/degrees C, cobalt) and high instantaneous dose rate [(0.26 +/- 0.01)%/degrees C, pulsed radiation]. Sufficient preirradiation can eliminate dose rate dependence of the temperature coefficient. On the contrary, preirradiation cannot eliminate dose rate dependence of the diode sensitivity itself.

Edema-induced increase in tumour cell survival for 125I and 103Pd prostate permanent seed implants—a bio-mathematical model

Edema caused by the surgical procedure of prostate seed implantation expands the source-to-point distances within the prostate and hence decreases the dose coverage. The decrease of dose coverage results in an increase in tumour cell survival. To investigate the effects of edema on tumour cell survival, a bio-mathematical model of edema and the corresponding cell killing by continuous low dose rate irradiation (CLDRI) was developed so that tumour cell surviving fractions can be estimated in an edematous prostate for both 125I and 103Pd seed implants. The dynamic nature of edema and its resolution were modelled with an exponential function V(T) = Vp (1 + M exp(−0.693T/Te)) where Vp is the prostate volume before implantation, M is the edema magnitude and Te is edema half-life (EHL). The dose rate of a radioactive seed was calculated according to AAPM TG43, i.e. Ḋ = SkΛg(r) ϕ̄an/r2, where r is the distance between a seed and a given point. The distance r is now a function of time because of edema. The g(r) was approximated as 1/r0.4 and 1/r0.8 for 125I and 103Pd, respectively. By expanding the mathematical expression of the resultant dose rate in a Taylor series of exponential functions of time, the dose rate was made equivalent to that produced from multiple fictitious radionuclides of different decay constants and strengths. The biologically effective dose (BED) for an edematous prostate implant was then calculated using a generalized Dale equation. The cell surviving fraction was computed as exp(−αBED), where α is the linear coefficient of the survival curve. The tumour cell survival was calculated for both 125I and 103Pd seed implants and for different tumour potential doubling time (TPDT) (from 5 days to 30 days) and for edemas of different magnitudes (from 0% to 95%) and edema half-lives (from 4 days to 30 days). Tumour cell survival increased with the increase of edema magnitude and EHL. For a typical edema of a half-life of 10 days and a magnitude of 50%, the edema increased tumour cell survival by about 1 and 2 orders of magnitude for 125I and 103Pd seed implants respectively. At the extreme (95% edema magnitude and an edema half-life of 30 days), the increase was more than 3 and 5 orders of magnitude for 125I and 103Pd seed implants respectively. The absolute increases were almost independent of TPDT and the prostate edema did not significantly change the effective treatment time. Tumour cell survival for prostate undergoing CLDRI using 125I or 103Pd seeds may be increased substantially due to the presence of edema caused by surgical trauma. This effect appears to be more pronounced for 103Pd than 125I because of the shorter half-life of 103Pd. If significant edema is observed post implantation, then a boost to the prostate using external beam radiotherapy may be considered as a part of the treatment strategy.

Gelation, swelling and water vapor permeability behavior of radiation synthesized poly(ethylene oxide) hydrogels

In this study, gamma ray induced gelation of aqueous solutions of poly(ethylene oxide), (PEO) with 73.300 Da average molecular weight has been studied. Percent of conversion of polymer into gel as well as swelling behavior were investigated gravimetrically. The effect of the dose rate on these properties was studied. Within the dose rate range studied, it is observed that low dose rate irradiation favors chain scission and although the dominant effect is still crosslinking, %gelation at a given dose decreases. Water vapor permeability (Wvp) of PEO hydrogels has been studied with regard to crosslink density changes and temperature. The water vapor permeability of hydrogels obtained at high dose rate was found to be lower than those obtained at low dose rate which was related to higher crosslink density achieved under higher dose rate irradiations.

The study of light yield increase after low dose rate irradiation in Y 3+ doping PbWO 4 crystals

Although trivalent ions (such as La 3+, Lu 3+ and Y 3+) doping can significantly improve the radiation hardness of lead tungstate crystals, some Y 3+ doping PbWO 4 (PWO) crystals showed exceptional irradiation behavior, namely, light yield increase after low dose rate irradiation. In addition the radiation hardness was sensitive to annealing temperature. In this study, we chose typical Y 3+ doping crystal samples and investigated the relationship between transmission, light yield and radiation hardness. The experimental results show that high temperature annealing can enhance the absorption band around 430 nm, while annealing at 50°C produces different results and can suppress this exceptional behavior. Light output increase not only exists in the top side of the boule, but also in the seed side, and is accompanied with optical transmission change in the wavelengths from 380 nm to about 500 nm simultaneously. The pre-existing 430 nm color centers in as-grown PWO:Y 3+ or annealing induced ones are unstable and can be “bleached” by low dose rate irradiation. The results of annealing and irradiation experiments of the samples show that the radiation hardness phenomenon was sensitive to annealing temperature, and thus a proper annealing temperature for PWO crystals was determined.

Combined modality radioimmunotherapy. Promise and peril.

Single-agent radioimmunotherapy (RIT), although potentially useful for slowing solid tumor growth, has not been effective in curing aggressive tumors, such as breast cancer. These cancers typically have p53 mutations and are less susceptible to apoptosis, the apparent mechanism of cell death from low dose-rate radiation. Thus, synergistic or combined modality radioimmunotherapy (CMRIT) agents are needed to increase radiosensitivity for therapeutic enhancement without additive toxicity. To assess synergy in CMRIT in a breast cancer xenograft model, we evaluated RGD peptide EMD 121974, an inhibitor of alpha(v)beta(3) integrin; paclitaxel, an antimicrotubule; IMC-C225, a monoclonal antibody to epidermal growth factor receptor (EGFR); and bcl-2 antisense oligonucleotide G3139. Groups of mice received (90)Y-DOTA-ChL6 in combination with each agent. Tumor size, survival, and blood counts were monitored for efficacy and toxicity. Immunopathologic evaluation of apoptosis was performed at selected time points after RIT and RIT + RGD CMRIT. CMRIT with RGD peptide increased apoptosis and resulted in 57% cures, compared with 0% cures with RIT alone. CMRIT with paclitaxel after RIT increased cures to 88%, compared with 25% cures with RIT before paclitaxel administration. CMRIT with IMC-C225 resulted in up to 20% cures if given before RIT. A time-dependent increase in toxicity was observed with IMC-C225 after RIT. CMRIT with bcl-2 antisense G3139 resulted in no cures and an increased rate of regrowth compared with RIT alone. Some combined modality therapies resulted in higher numbers of cures, while others decreased cures and responses and increased toxicity compared with RIT alone. These results support the potential for CMRIT but illustrate the complexity of predicting the efficacy and toxicity and the importance of the relationship between dose and sequence of administration.

The optimal fraction size in high-dose-rate brachytherapy: dependency on tissue repair kinetics and low-dose rate

Background and Purpose : Indications of the existence of long repair half-times on the order of 2–4 h for late-responding human normal tissues have been obtained from continuous hyperfractionated accelerated radiotherapy (CHART). Recently, these data were used to explain, on the basis of the biologically effective dose (BED), the potential superiority of fractionated high-dose rate (HDR) with large fraction sizes of 5–7 Gy over continuous low-dose rate (LDR) irradiation at 0.5 Gy/h in cervical carcinoma. We investigated the optimal fraction size in HDR brachytherapy and its dependency on treatment choices (overall treatment time, number of HDR fractions, and time interval between fractions) and treatment conditions (reference low-dose rate, tissue repair characteristics). Methods and Materials : Radiobiologic model calculations were performed using the linear-quadratic model for incomplete mono-exponential repair. An irradiation dose of 20 Gy was assumed to be applied either with HDR in 2–12 fractions or continuously with LDR for a range of dose rates. HDR and LDR treatment regimens were compared on the basis of the BED and BED ratio of normal tissue and tumor, assuming repair half-times between 1 h and 4 h. Results : With the assumption that the repair half-time of normal tissue was three times longer than that of the tumor, hypofractionation in HDR relative to LDR could result in relative normal tissue sparing if the optimum fraction size is selected. By dose reduction while keeping the tumor BED constant, absolute normal tissue sparing might therefore be achieved. This optimum HDR fraction size was found to be largely dependent on the LDR dose rate. On the basis of the BED NT/TUM ratio of HDR over LDR, 3 × 6.7 Gy would be the optimal HDR fractionation scheme for replacement of an LDR scheme of 20 Gy in 10–30 h (dose rate 2–0.67 Gy/h), while at a lower dose rate of 0.5 Gy/h, four fractions of 5 Gy would be preferential, still assuming large differences between tumor and normal tissue repair half-times and equal overall treatment time. For the same fraction size, an even larger normal tissue sparing can be obtained by prolongation of the HDR overall treatment time. Conclusion : Radiobiologic model calculations presented here aim to demonstrate that hypofractionation in HDR might have its opportunities for widening the therapeutic window, but definitely has its limits. For each specific combination of the parameters, a theoretical optimal HDR fraction size with regard to relative or absolute normal tissue sparing can be estimated, but because of uncertainty in the biologic parameters, these hypofractionation schemes cannot be generalized for all HDR brachytherapy indications.

Effect of subsequent acute-dose irradiation on cell survival in vitro following low dose-rate exposures

Purpose : Following acute irradiation, excess radiosensitivity is generally seen at doses <1 Gy, a phenomenon termed 'low-dose hyper-radiosensitivity' (HRS). A very strong, HRS-like inverse dose-rate effect has also been described following continuous low dose-rate (LDR) irradiation at <30 cGy h -1. We report on the sequential irradiation of a cell line by such LDR exposures followed by low acute doses, where either treatment individually would elicit a hypersensitive response. The aim was to determine if a prior LDR exposure would remove the HRS normally seen in response to very small acute radiation doses. Materials and methods : T98G human glioma cells were given single continuous LDR exposures of 5-60 cGy h -1 using a 60 Co γ-source. At intervals of 0 or 4 h following LDR irradiation, cells were further irradiated with a range of acute doses using 240-kVp X-rays. The response to the combined treatment was assessed using high-precision clonogenic cell survival assays, and the amount of HRS at acute doses <1 Gy was determined. Results : LDR at ≥60 cGy h -1 to total doses up to 5 Gy in asynchronously growing cells did not remove HRS in the subsequent acute-dose survival curve. In confluent cultures, subsequent acute-dose HRS was not present after an LDR dose of 5 Gy at either 60 or 30 cGy h -1, but returned if a 4-h interval was left between LDR and acute-dose irradiation. In confluent cultures, acute-dose HRS remained for LDR treatments at 5 or 10 cGy h -1 or if the total dose was 2 Gy. Taking all cultures and dose-rates together, the 'degree' of acute-dose HRS, as measured by α s, was significantly greater in cells irradiated at LDR to a total dose of 2 than of 5Gy. Conclusions : Initial LDR exposure can affect a subsequent HRS response. HRS is reduced after LDR exposures at greater dose intensity, but can recover again within 4 h of completion of LDR exposure. This suggests that processes determining increased resistance to small acute doses (removal of HRS) might be governed by the level of repairable DNA lesions.

Micronuclei induced by low dose rate irradiation in early spermatids of p53 null and wild mice.

To obtain evidence of the dose-rate effect on induction of micronuclei in early spermatids, we observed frequencies in wild-type p53(+/+), heterozygous p53(+/-) and null p53(-/-) mice 14 days after gamma rays irradiation at a high (1,020 mGy/min) or a low (1.2 mGy/min) dose-rate. A dose- and dose-rate-related increase in micronuclei was seen in early spermatids with no difference between the different p53 status. These data were found to be best fitted by a linear-quadratic dose-response model at a high dose-rate, and by a linear dose-response model at a low dose-rate. The yields at 1.2 mGy/min were significantly lower than those at 1,020 mGy/min in the same manner, independent of p53 status. Testis weight declined significantly after 3 Gy irradiation, but did not depend on dose-rates. In our other studies, we observed the complete elimination both of malformation in fetuses and CD3- 4+ mutant T-lymphocytes in p53(+/+) mice, but not in p53(-/-) mice after irradiation. This indicates that concerted DNA repair and p53-dependent apoptosis are likely to completely eliminate mutagenic damage from the irradiated tissues at low doses or dose-rates in teratogenesis and lymphocytes. In the germ cell, however, irradiation at 1.2 mGy/min was mutagenic, independent of p53 status.

Biological effectiveness of isolated short electron tracks: V79-4 cell inactivation following low dose-rate irradiation with Al K ultrasoft X-rays

Purpose : To investigate the biological effect of single, isolated, short electron tracks (<70 nm) relevant to practical human exposures to low-linear energy transfer radiation. Materials and methods : An irradiation rig was constructed that allowed environmentally controlled, protracted irradiations with an individually prescribed dose to up to 20 samples over a period of days. Inactivation of V79-4 mammalian cells by Al K ultrasoft X-rays was studied at high and low dose-rates with a maximum exposure time of 42 h. Results : A significant increase in clonogenic survival was observed at the higher doses when the exposure time was increased from <6 min to 21 h, with no further increase observed for 42-h exposures. Despite the short range of the low-energy electrons produced (<70 nm), significant cell inactivation was observed for these low dose-rate exposures. Conclusions : The results are consistent with the hypothesis that even individual tracks can be biologically effective.

Radiation-induced apoptosis in the scid mouse spleen after low dose-rate irradiation

Purpose : To elucidate the process of radioadaptation, the role of DNA-PK activity was examined using the scid mouse defective in DNA-PKcs. Materials and methods : The induction of apoptosis in the spleens of the C.B-17 Icr scid mouse and the parental mouse was studied after chronic irradiation with γ-rays at 1.5 Gy (0.001Gy min -1 for 25 h) followed by challenge irradiation with X-rays at 3.0 Gy (1.0 Gy min -1 for 3 min). Results : When the wild-type mouse was previously exposed to chronic irradiation (1.5Gy) at a low dose-rate (0.001 Gy min -1) , apoptosis induced by acute irradiation (3.0 Gy, 1.0Gy min -1) was significantly suppressed, especially in the splenic white pulp. There was no change by acute irradiation after chronic irradiation in the scid mouse, although an effect was detected in the spleen after acute irradiation alone. Conclusions : These data suggest that DNA-PK activity might play a major role in the radioadaptive response following pre-irradiation at a low dose-rate.

Mathematical model for assessment of radiation risk on long space missions

A mathematical model is developed which describes the dynamics of radiation-induced mortality in mammalian populations. It relates statistical biometric functions with statistical characteristics and dynamics of an organism's critical system. In the framework of the model the effects of low and very low dose rates of chronic radiation on mice are simulated. Respectively, thrombocytopoietic and granulocytopoietic systems are considered as the critical ones. To calculate the dynamics of these systems, mathematical models are applied, too. In accordance with experimental data, the mortality model reproduces on quantitative level both increased and decreased mortality rates in populations of LAF 1 mice, which were chronically exposed, respectively, to low and very low level radiation. All this makes it feasible to use the model as a basis for risk assessments of low level long-term irradiation.

Enhanced levels of deoxycytidine kinase and thymidine kinase 1 and 2 after pulsed low dose rate irradiation as an adaptive response to radiation

After pulsed low dose rate irradiation the activities of deoxycytidine kinase and thymidine kinase 1 and 2 were increased 1.5-2-fold 6 h after treatment. Twenty-four hours after treatment the activities of these enzymes had returned to control levels. We presume that the increase of enzyme activities is part of an adaptive response to irradiation and that this increase could be an explanation for the increased survival in the initial part of the SW-1573 cell survival curve. The observation that not only S-phase specific thymidine kinase 1 but also mitochondrial thymidine kinase 2 increases, implies that both these enzymes play a role in an adaptive response of cells to irradiation.

Chromosomal radiosensitivity study of temporary nuclear workers and the support of the adaptive response induced by occupational exposure

Purpose : To study chromosomal radiosensitivity in a population of radiation workers and investigate the possibility of an adaptive response in lymphocytes of workers after short-term occupational exposure to ionizing radiation. Materials and methods : The studied group comprised 41 workers temporarily employed at the Nuclear Power Plant Doel (Belgium) for reactor maintenance. A blood sample was taken before and directly after the exposure period of about 1 month. Chromosomal radiosensitivity was assessed in vitro by the G2 assay and the G0 micronucleus (MN) assay. For the MN assay, a low dose-rate (LDR) in vitro irradiation protocol was applied in addition to high dose-rate (HDR) irradiation of the blood samples in order to determine the dose-rate sparing (DRS) effect. Results : No statistically significant effect of the occupational exposures (up to 10 mSv) on the baseline MN frequencies without in vitro irradiation was observed. A comparison of the number of chromatid aberrations pre- and post-exposure shows no effect of the occupational exposure. On the other hand, the G0-MN assay with the LDR irradiation protocol reveals a systematic reduction in chromosomal radiosensitivity by the exposure, increasing with dose. For workers who received the highest dose (4-10 mSv) a statistically significant (p < 0.05) decrease of the in vitro induced MN yields and increase of the dose-rate sparing was observed. Conclusions : Short-term low-dose occupational exposure may act as an in vivo adaptive dose and stimulate repair in G0 lymphocytes.

Dose and dose rate effects of whole-body proton irradiation on leukocyte populations and lymphoid organs: Part I

The goal of part I of this study was to evaluate the effects of whole-body proton irradiation on lymphoid organs and specific leukocyte populations. C57BL/6 mice were exposed to the entry region of the proton Bragg curve to total doses of 0.5 gray (Gy), 1.5 Gy, and 3.0 Gy, each delivered at a low dose rate (LDR) of 1 cGy/min and high dose rate (HDR) of 80 cGy/min. Non-irradiated and 3 Gy HDR γ-irradiated groups were included as controls. At 4 days post-irradiation, highly significant radiation dose-dependent reductions were observed in the mass of both lymphoid organs and the numbers of leukocytes and T (CD3 +), T helper (CD3 +/CD4 +), T cytotoxic (CD3 +/CD8 +), and B (CD19 +) cells in both blood and spleen. A less pronounced dose effect was noted for natural killer (NK1.1 + NK) cells in spleen. Monocyte, but not granulocyte, counts in blood were highly dose-dependent. The numbers for each population generally tended to be lower with HDR than with LDR radiation; a significant dose rate effect was found in the percentages of T and B cells, monocytes, and granulocytes and in CD4 +:CD8 + ratios. These data indicate that mononuclear cell response to the entry region of the proton Bragg curve is highly dependent upon the total dose and that dose rate effects are evident with some cell types. Results from γ- and proton-irradiated groups (both at 3 Gy HDR) were similar, although proton-irradiation gave consistently lower values in some measurements.

Commentary on “Intraluminal Brachytherapy for Malignant Endobronchial Tumors: An Update on Low-Dose Rate Versus High-Dose Rate Radiation Therapy”

Commentary on “Intraluminal Brachytherapy for Malignant Endobronchial Tumors: An Update on Low-Dose Rate Versus High-Dose Rate Radiation Therapy”

Development of microbeam irradiation system for radiobiology

In order to evaluate the risk of low dose or low dose rate irradiation, a microbeam irradiation system has been proposed, which overcomes the difficulty due to the Poisson distribution of hit-cell in the majority of non-hit cell population. Designed system has the following specifications; proposed X-ray beam size is 1 μm which is small enough to aim at cell nucleus (a few microns) in the energy range of from 5 to 10 keV; cells grown on a specially designed dish are automatically recognized and individually irradiated with vertically deflected upward beam through the film; cell recognition and irradiation are performed automatically with speed of more than 1000 cells/h.

Apoptosis-related gene and protein expression in human lymphoma xenografts (Raji) after low dose rate radiation using 67Cu-2IT-BAT-Lym-1 radioimmunotherapy.

Despite low radiation dose rates, radioimmunotherapy (RIT) has proven particularly effective in the treatment of malignancies, such as lymphoma. Apoptosis has been suggested to be a major mechanism for cell death from continuous low-dose rate radiation from radioimmunotherapy. The goal of this study was to examine Raji lymphoma xenografts for induction of apoptosis and modulation of apoptosis-related gene and protein expression in response to 67Cu-2IT-BAT-Lym-1 RIT. In preclinical and clinical trials, 67Cu-2IT-BAT-Lym-1 has shown an exceptionally long tumor residence time associated with substantial cumulated radiation doses. The Raji model mirrors human lymphomas that have mutant p53 and increased BCL2 expression. Untreated athymic BALB/c nu/nu mice and mice treated with 400 micrograms Lym-1, or 335-500 microCi 67Cu on less than 400 micrograms Lym-1 antibody, were observed for toxicity and response over 84 days. Subgroups of 4-5 mice were sacrificed at 3, 6 and 24 h after therapy so that tumors could be examined for poly(ADP-ribose) polymerase (PARP) and DNA ladder evidence for apoptosis and for BCL2, p53, p21, GADD45, TGF-beta 1 and c-MYC gene and protein expression. Untreated tumors had little evidence of apoptosis and Lym-1 had no effect on apoptosis or gene expression. 67Cu-2IT-BAT-Lym-1 RIT induced an overall response rate of 50% with tolerable toxicity, and 29% of the tumors were cured at cumulated tumor radiation doses of about 1800 cGy. Apoptosis was greatly increased in the RIT treated Raji xenografts as evidenced by cleavage of PARP to the characteristic 85 kD fragment at 3 and 6 h and by the DNA cleavage pattern. BCL2 gene and protein expression were substantially decreased at 3 and 24 h, respectively, after 67Cu-2IT-BAT-Lym-1 RIT despite only modest cumulated radiation doses (56 cGy at 3 h). Evidence for apoptosis preceded tumor regression by 4-6 days. In these therapy-resistant, human lymphoma tumors treated with 67Cu-2IT-BAT-Lym-1, apoptosis was convincingly demonstrated to be a major mechanism for the effectiveness of RIT and occurred by p53-independent mechanisms.

IUdR polymers for combined continuous low-dose rate and high-dose rate sensitization of experimental human malignant gliomas.

Local polymeric delivery enhances IUdR radiosensitization of human malignant gliomas (MG). The combined low-dose rate (LDR) (0.03 Gy/h) and fractionated high-dose rate (HDR) treatments result in cures of experimental MGs. To enhance efficacy, we combined polymeric IUdR delivery, LDR, and HDR for treatments of both subcutaneous and intracranial MGs. In vitro: Cells (U251 MG) were trypsinized and replated in triplicate 1 day prior to LDR irradiation in media either without (control) or with 10 microM IUdR. After 72 hr, LDR irradiation cells were acutely irradiated (1.1 Gy/min) with increasing (0, 1.25, 2.5, 5.0, or 10 Gy) single doses. Implantable IUdR polymers [(poly(bis(p-carboxyphenoxy)-propane) (PCPP): sebaic acid (PCPP:SA), 20:80] (50% loading; 10 mg) were synthesized. In vivo: For flank vs. intracranial tumors, mice had 6 x 10(6) subcutaneous vs. 2 x 10(5) intracranial cells. For intracranial or subcutaneous MGs, mice had intratumoral blank (empty) vs. IUdR polymer treatments. One day after implantation, mice had immediate external LDR (3 cGy/h x 3 days total body irradiation) or HDR (2 Gy BID x 4 days to tumor site) or concurrent treatments. For the in vitro IUdR treatments, LDR resulted in a striking increase in cell-killing when combined with HDR. For the in vivo LDR treatments of flank tumors, the growth delay was greater for the IUdR vs. blank polymer treatments. For the combined LDR and HDR, the IUdR treatments resulted in a dramatic decrease in tumor volumes. On day 60 the log V/V0 were -1.7 +/- 0.22 for combined LDR + HDR + IUdR polymer (P < 0.05 vs. combined LDR + HDR + blank polymer). Survival for the intracranial controls was 22.9 +/- 1.2 days. For the blank polymer + LDR vs. blank polymer + LDR + HDR treatments, survival was 25.3 +/- 1.7 (P = NS) vs. 48.1 +/- 3.5 days (P < 0.05). For IUdR polymer + LDR treatment survival was 27.3 +/- 2.3 days (P = NS). The most striking improvement in survival followed the IUdR polymer + LDR + HDR treatment: 66.0 + 6.4 days (P < 0.05 vs. blank polymer + LDR + HDR). The polymeric IUdR delivery plus combined continuous LDR and HDR treatments results in growth delay and improved survival in animals bearing the MG xenografts. This treatment may hold promise for the treatment of human MGs.

Workshop on Comparative Radiobiology and Protection of theEnvironment Dublin, 21-24 October 2000

Workshop on Comparative Radiobiology and Protection of theEnvironment Dublin, 21-24 October 2000