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High-grade gliomas, such as glioblastoma (GBM) and diffuse intrinsic pontine glioma (DIPG), are characterized by an aggressive phenotype with nearly universal local disease progression despite multimodal treatment, which typically includes chemotherapy, radiotherapy, and possibly surgery. Radiosensitizers that have improved the effects of radiotherapy for extracranial tumors have been ineffective for the treatment of GBM and DIPG, in part due to poor blood-brain barrier penetration and rapid intracranial clearance of small molecules. Here, we demonstrate that nanoparticles can provide sustained drug release and minimal toxicity. When administered locally, these nanoparticles conferred radiosensitization in vitro and improved survival in rats with intracranial gliomas when delivered concurrently with a 5-day course of fractionated radiotherapy. Compared with previous work using locally delivered radiosensitizers and cranial radiation, our approach, based on the rational selection of agents and a clinically relevant radiation dosing schedule, produces the strongest synergistic effects between chemo- and radiotherapy approaches to the treatment of high-grade gliomas. Mol Cancer Ther; 16(8); 1456-69. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Purpose: To measure the dosimetric properties of the Model AgX100 ¹²⁵I source for interstitial brachytherapy., Methods and Materials: The photon energy spectrum emitted by the AgX100 source was measured using a high-resolution germanium spectrometer customized for low-energy brachytherapy source spectrometry. The dose distribution around the source was measured using the 1×1×1 mm³ lithium fluoride thermoluminescent dosimeters in water-equivalent solid phantoms. The dosimetric parameters needed for dose calculation using the American Association of Physicists in Medicine Task Group No. 43 (TG-43) formalism were determined and compared with the results of a Monte Carlo simulation by an independent research group and with the TG-43 consensus values of the well-established model 6711 source., Results: It was found that (1) the photon energy spectrum emitted by the AgX100 source was nearly identical to that emitted by the model 6711, (2) the dose-rate constant determined by the photon spectrometry technique (0.957±0.037 cGy·h⁻¹·U⁻¹) and by the thermoluminescent dosimeter technique (0.995±0.066 cGy·h⁻¹·U⁻¹) was within 1.5% of the corresponding values determined for the model 6711 source, and (3) the radial dose function and the anisotropy function of the AgX100 source were also found to be similar to the consensus data established for the model 6711 source in the TG-43 update report., Conclusions: A comprehensive dosimetric characterization has been carried out for the model AgX100 ¹²⁵I source. The American Association of Physicists in Medicine TG-43 dosimetry parameters for this source has been determined from the experimental data., (Copyright © 2012 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the utility and accuracy of high-sensitivity TLD for dosimetric characterization of low-energy brachytherapy sources., Methods: One hundred high-sensitivity (TLD-100H) and 100 normal-sensitivity (TLD-100) TLDs were used in this study. The TLD-100s were annealed at 400°C for one hour and then kept at room temperature for 45 minutes followed by 80°C heating for 24 hours. To prevent temperature overshot from reducing the sensitivity of TLD-100Hs, a novel thermal reservoir was built, tested, and used to anneal TLD-100H at 240 0C for 15 minutes and then kept at room temperature for 45 minutes followed by 100 0C heating for one hour. These TLDs were then irradiated uniformly in a large cavity Cs-137 irradiator for biomedical research (Shepherd, Mark III) to test their reproducibility and to establish their relative sensitivities. The radial dose function of a Model AgX100 125I source was measured using both types of TLDs in water-equivalent solid phantoms as a test case. The radial dose function measured by the TLD-100H was compared with that measured by TLD-100 to determine its utility in brachytherapy dosimetry characterization., Results: Consistent and accurate annealing of high-sensitivity TLDs was achieved by using a custom-built thermal reservoir system. TLD-100H was found to be about 18 times more sensitive than TLD-100. For a 125I source with a source-strength of 2.7U, the irradiation time for radial dose function characterization up to 7 cm can be cut down from 38 days to 3 days. The radial dose function measured by TLD-100H agreed well (within ±6%) with that measured by TLD-100., Conclusions: A novel thermal reservoir was used for consistent annealing of high-sensitivity TLDs. TLD-100H can significantly shorten the irradiation time needed for a complete characterization of radial dose function. Investigation of TLD-100H for complete brachytherapy source characterization is in progress. Supported in part by NIH grant R01-CA134627., (© 2012 American Association of Physicists in Medicine.)

Purpose: To develop and characterize a novel thermal reservoir for consistent and accurate annealing of high-sensitivity thermoluminescence dosimeters (TLD-100H) for dosimetry of brachytherapy sources., Methods: The sensitivity of TLD-100H is about 18 times that of TLD-100 which has clear advantages in for interstitial brachytherapy sources. However, the TLD-100H requires a short high temperature annealing cycle (15 min.) and opening and closing the oven door causes significant temperature fluctuations leading to unreliable measurements. A new thermal reservoir made of aluminum alloy was developed to provide stable temperature environment in a standard hot air oven. The thermal reservoir consisted of a 20 cm × 20 cm × 8 cm Al block with a machine-milled chamber in the middle to house the aluminum TLD holding tray. The thermal reservoir was placed inside the oven until it reaches thermal equilibrium with oven chamber. The temperatures of the oven chamber, heat reservoir, and TLD holding tray were monitored by two independent thermo-couples which interfaced digitally to a control computer. A LabView interface was written for monitoring and recording the temperatures in TLD holding tray, the thermal reservoir, and oven chamber. The temperature profiles were measured as a function of oven-door open duration. The settings for oven chamber temperature and oven door open-close duration were optimized to achieve a stable temperature of 240 0C in the TLD holding tray. Complete temperature profiles of the TLD annealing tray over the entire annealing process were obtained., Results: A LabView interface was written for monitoring and recording the temperatures in TLD holding The use of the thermal reservoir has significantly reduced the temperature fluctuations caused by the opening of oven door when inserting the TLD holding tray into the oven chamber. It has enabled consistent annealing of high-sensitivity TLDs., Conclusions: A comprehensive characterization of a custom-built novel thermal reservoir for annealing high-sensitivity TLD has been carried out. It enabled consistent and accurate annealing of high- sensitivity TLDs which could significantly improve the efficiency of brachytherapy source characterizations. Supported in part by NIH grant R01-CA134627., (© 2012 American Association of Physicists in Medicine.)

Purpose: Since its introduction in 2004, the model CS-1 Rev.1 131Cs source has been used in many radiation therapy clinics for prostate brachytherapy. In 2006, this source model underwent a Rev.2 production revision. The aim of this work was to investigate the dosimetric influences of the Rev.2 production revision using high-resolution photon spectrometry., Methods: Three CS-1 Rev.1 and three CS-1 Rev.2 131Cs sources were used in this study. The relative photon energy spectrum emitted by each source in the transverse bisector of the source was measured using a high-resolution germanium detector designed for low-energy photon spectrometry. Based on the measured photon energy spectrum and the radioactivity distribution in the source, the dose-rate constant (lamda) of each source was determined. The effects of the Rev.2 production revision were quantified by comparing the emitted photon energy spectra and the lamda values determined for the sources manufactured before and after the production revision., Results: The relative photon energy spectrum originating from the principal emissions of 131Cs was found to be nearly identical before and after the Rev.2 revision. However, the portion of the spectrum originating from the production of fluorescent x rays in niobium, a trace element present in the source construction materials, was found to differ significantly between the Rev.1 and Rev.2 sources. The peak intensity of the Nb Kalpha and Nb Kbeta fluorescent x rays from the Rev.2 source was approximately 35% of that from the Rev.1 source. Consequently, the nominal lamda value of the Rev.2 source was found to be greater than that determined for the Rev.1 source by approximately 0.7% +/- 0.5%., Conclusions: A significant reduction (65%) in relative niobium fluorescent x-ray yield was observed in the Rev.2 131Cs sources. The impact of this reduction on the dose-rate constant was found to be small, with a relative difference of less than 1%. This study demonstrates that photon spectrometry can be used as a sensitive and convenient tool for monitoring and for quantifying the dosimetric effects of brachytherapy source-production revisions. Because production revision can change both the geometry and the atomic composition of brachytherapy sources, its dosimetric impact should be carefully monitored and evaluated for each production revision.

Purpose: Although several dosimetric characterizations using Monte Carlo simulation and thermoluminescent dosimetry (TLD) have been reported for the new Advantage Pd-103 source (IsoAid, LLC, Port Richey, FL), no AAPM consensus value has been established for the dosimetric parameters of the source. The aim of this work was to perform an additional dose-rate constant (lamda) determination using a recently established photon spectrometry technique (PST) that is independent of the published TLD and Monte Carlo techniques., Methods: Three Model IAPD-103A Advantage Pd-103 sources were used in this study. The relative photon energy spectrum emitted by each source along the transverse axis was measured using a high-resolution germanium spectrometer designed for low-energy photons. For each source, the dose-rate constant was determined from its emitted energy spectrum. The PST-determined dose-rate constant (PST lamda) was then compared to those determined by TLD (TLD lamda) and Monte Carlo (MC lamda) techniques. A likely consensus lamda value was estimated as the arithmetic mean of the average lamda values determined by each of three different techniques., Results: The average PST lamda value for the three Advantage sources was found to be (0.676 +.- 0.026) cGyh(-1) U(-1). Intersource variation in PST lamda was less than 0.01%. The PST lamda was within 2% of the reported MC lamda values determined by PTRAN, EGSnrc, and MCNP5 codes. It was 3.4% lower than the reported TLD lamda. A likely consensus lamda value was estimated to be (0.688 +/- 0.026) cGyh(-1) U(-1), similar to the AAPM consensus values recommended currently for the Theragenics (Buford, GA) Model 200 (0.686 +/- 0.033) cGyh(-1) U(-1), the NASI (Chatsworth, CA) Model MED3633 (0.688 +/- 0.033) cGyh(-1) U(-1), and the Best Medical (Springfield, VA) Model 2335 (0.685 +/- 0.033) cGyh(-1) U(-1) 103Pd sources., Conclusions: An independent lamda determination has been performed for the Advantage Pd-103 source. The PST lamda obtained in this work provides additional information needed for establishing a more accurate consensus lamda value for the Advantage Pd-103 source.

The aim of this work was to conduct an independent determination of the dose rate constant of the newly introduced Model CS-1 131Cs seed. A total of eight 131Cs seeds were obtained from the seed manufacturer. The air-kerma strength of each seed was measured by the manufacturer whose calibration is traceable to the air-kerma strength standard established for the 131Cs seeds at the National Institute of Standards and Technology (1 sigma uncertainty < 1%). The dose rate constant of each seed was measured by two independent methods: One based on the actual photon energy spectrum emitted by the seed using gamma-ray spectrometry and the other based on the dose-rate measured by thermoluminescent dosimeter (TLD) in a Solid Water phantom. The dose rate constant in water determined by the gamma-ray spectrometry technique and by the TLD dosimetry are 1.066 +/- 0.064 cGyh(-1)U(-1) and 1.058 +/- 0.106 cGyh(-1)U(-1), respectively, showing excellent agreement with each other. These values, however, are approximately 15% greater than a previously reported value of 0.915 cGyh(-1)U(-1) [Med. Phys. 31, 1529-1538 (2004)]. Although low-energy fluorescent x rays at 16.6 and 18.7 keV, originating from niobium present in the seed construction, were measured in the energy spectrum of the 131Cs seeds, their yields were not sufficient to lower the dose rate constant to the value of 0.915 cGyh(-1)U(-1). Additional determinations of the dose rate constant may be needed to establish an AAPM recommended consensus value for routine clinical use of the 131Cs seed.

Purpose: To measure the relative biological effectiveness (RBE) of continuous low dose rate irradiation (CLDRI) using 103Pd sources relative to acute high dose rate irradiations (AHDRI) from a 250 kVp x-ray beam and an x-ray beam having an equivalent mono-energetic photon energy equal to the average energy of the 103Pd source for BA1112 rhabdomyosarcoma cells., Materials and Methods: A customized 103Pd irradiator was built to provide CLDRI using 103Pd at different dose rates relevant to clinical interstitial brachytherapy to BA1112 rhabdomyosarcoma cells growing in exponential phase in culture. A special x-ray beam that simulates the photon energies emitted by the 103Pd source was also developed to provide acute high dose rate irradiation at those energies. Cell survival curves from different irradiation conditions were measured. The RBE with respect to AHDRI using standard 250 kVp x-rays was determined from the doses required to achieve a cell surviving faction of 0.01., Results: For acute irradiation, the RBE of the x-rays simulating (103)Pd was 1.24 relative to 250 kVp x-rays. A profound dose rate effect was observed at low dose rates in the range of 6.8 - 14.4 cGy/h that are typical of permanent interstitial brachytherapy. At cell-surviving fraction of 0.01, the RBE of CLDRI at 6.8 and 14.4 cGy/h using 103Pd sources was reduced by a factor of 3 and 2, respectively, relative to the acute exposure. This observation is in good agreement with recent in vivo tumor cure studies performed on BA1112 tumor., Conclusion: The relative biological effectiveness of the photons emitted by 103Pd depends on both the linear energy transfer (LET) of the low energy photons and the dose rate of the irradiation. The higher LET of 103Pd photons is biologically more effective in killing BA1112 tumor cells compared to conventional 250 kVp x-rays when both are delivered at the same dose rate. But the gain in RBE that results from the higher LET can be quickly negated by the reduced dose rate of the irradiation.

Purpose: To develop an experimental technique for studying the radiobiology of continuous low-dose-rate irradiation (CLDRI) using clinical brachytherapy sources emitting low energy photons for a rat solid tumor model., Methods and Materials: BA1112 tumors were grown between the ears of 14-week-old male WAG/Rij rats by interdermal inoculation. A radioactive source afterloading system, which consists of a lightweight helmet sutured to the rat and a nine-source polystyrene applicator, was fabricated for in vivo tumor irradiation by (125)I and (103)Pd brachytherapy sources. This system has a 12 x 12 mm opening in the center to accommodate the tumor and its growth during irradiation (the diameter of a typical BA1112 tumor was about 6 mm when radiation was applied). The spatial locations of the nine sources were optimized to produce an as uniform as possible three-dimensional dose distribution to the central portion of the applicator for both the (125)I and (103)Pd sources. Absolute dose delivered by the applicator was verified by point dose measurements using calibrated TLD in a polystyrene phantom that mimics the scattering environment of the tumor on the rat., Results: The feasibility of tumor cure experiments using the experimental technique presented in this work was demonstrated. The technique was used to study the influence of initial dose rate on the in vivo tumor cure probability of BA1112 tumors irradiated by (125)I and (103)Pd sources at dose rates varying from 8-20 cGy/h. The technique was also used for studying the in vitro tumor cell survival following in vivo CLDRI irradiation of the tumor., Conclusion: An experimental technique using an in vivo tumor model has been developed for studying the radiobiological effects of continuous low-dose-rate irradiations using (125)I sources alone, (103)Pd sources alone, or a mixture of (125)I and (103)Pd sources.

Recent developments in the past two years require a significant change in the dosimetry of 103Pd brachytherapy sources (Theraseed model 200, manufactured by Theragenics Corp., Atlanta, GA). Since their introduction in 1987, the air kerma strength of 103Pd sources for interstitial brachytherapy has been determined using a system of apparent activity measurement based upon the measurement of photon fluence at a reference distance along the transverse axis of the source free in air, using a NaI (T1) scintillation detector at the manufacturer's facilities. This detection system has been calibrated against a National Institute of Standards and Technology (NIST)-traceable activity standard of a 109Cd source. This system produced a highly consistent standard (within +/-2%) for over 12 years, with the exception of the last 109Cd source change in September 1997, which resulted in a change of 9% from the original 1987 standard. The second major development affecting 103Pd dosimetry is that on 13 January 1999 a primary national standard for the air kerma strength of 103Pd seeds was developed by NIST. This primary standard is based upon an absolute measurement of air kerma rate free in air at a reference distance from the source along its transverse axis using a wide angle free air chamber (WAFAC). In order to implement this new standard for the calibration of source strength in clinical dosimetry for interstitial implants, it is necessary to measure the dose-rate constant for the 103Pd seeds using a calibration of source strength based on the NIST 99 standard. In this work, a measurement of the dose-rate constant using lithium fluoride (LiF) thermoluminescent dosimeters (TLDs) in a water equivalent solid phantom is reported. The measured value of this constant is 0.65 +/- 0.05 cGy h(-1) U(-1), where the unit air kerma strength is 1 U = 1 cGy h(-1) cm2 = 1 microGy h(-1) m2, and is directly traceable to the NIST 99 standard. The implementation of the NIST 99 standard for 103Pd should be accompanied by a simultaneous adoption of the new dose-rate constant reported here. No changes in radial dose function, anisotropy function, anisotropy factor, and geometry function are needed. However, a change in prescribed dose may be necessary to deliver the same physical dose as before.

Single cell suspensions of Chinese hamster lung cells were treated with hematoporphyrin derivative (HPD) and were exposed under aerobic conditions to visible light alone, X rays alone or light and X rays concurrently. Cytotoxicity was assayed using the colony formation ability of cells as the end point. The drug toxicity, phototoxicity, radiosensitization and photoradiosensitization of HPD were examined for a drug concentration of 1 microgram/ml and incubation time of 24 h. In these experiments, the X-ray dose was 3 Gy and the energy fluence of visible light was 0.35 kJ/m2, and both irradiations lasted for 10 min. A significant enhancement in cytotoxicity was observed when the HPD-treated cells were irradiated concurrently with light and X rays. However, no significant enhancement was observed when visible-light and X irradiations were performed sequentially with a 15-min waiting time between the two irradiations.

This paper describes the development of sources, applicators, and techniques that can be used to irradiate rat rectums with continuous irradiation at dose rates of interest in brachytherapy, either with the full circumference of the rectum irradiated, or with half of the circumference shielded from the radiation. The system uses encapsulated 241Am sources, to irradiate rat rectum with 60 keV photons continuously at a dose rate of up to 50 cGy/hr. Details of the design and fabrication of the 241Am sources, the rectal applicator, the dosimetry of the system, and the protocols for preparing and irradiating the rats, and for detecting early rectal injury using histological examination of irradiated rectum are presented. Highly effective shielding (attenuation factors as low as 0.04) of half of the circumference of the rat rectum was achievable. Unidirectional 241Am irradiators for intracavitary brachytherapy offer a unique tool for examining the effects of shielding a portion of the circumference of the rat rectum, on the radiation tolerance of the rectum.

The dependence of iododeoxyuridine (IUdR) radiosensitization on photon energy and dose rate in the range of interest to brachytherapy was investigated by irradiating Chinese hamster cells in vitro under aerobic conditions. The radiosensitization produced by 10(-5) and 10(-4) M IUdR for 28-keV (average) photons from 125I, 60-keV photons from 241Am, and 830-keV (average) photons from 226Ra was measured at nominal dose rates of 0.17, 0.30, 0.57, and 0.73 Gy/h. Radiosensitization factors for IUdR were essentially independent of dose rate from 0.30 to 0.73 Gy/h for all cases except for 10(-4) M IUdR plus 241Am, in which case the radiosensitization factor increased from 2.5 +/- 0.2 to 3.0 +/- 0.1. In all cases, the radiosensitization factor decreased significantly as the dose rate was lowered from 0.30 to 0.17 Gy/h e.g., the radiosensitization factor for 241Am dropped to 1.9 +/- 0.2 at a dose rate of 0.17 Gy/h. Moreover, at 0.17 Gy/h the radiosensitization factors were essentially the same for all three photon energies. As the dose rate increased from 0.17 to 0.73 Gy/h, the difference between the radiosensitization factors for the three photon energies became larger; radiosensitization factors for 241Am were higher than those for 226Ra and 125I. In temporary brachytherapy the tumor is irradiated at the higher dose rate of about 0.50-0.70 Gy/h, while the normal tissues are irradiated at lower dose rates; the dose rate dependence of the radiosensitization factor may therefore lead to an improvement in the therapeutic ratio for brachytherapy in combination with IUdR.

The dependence of IUdR radiosensitization on photon energy was investigated by irradiating Chinese hamster cells in vitro under aerobic conditions at a dose rate of 0.72 Gy/hr which is typical of temporary brachytherapy implants. It had been observed previously that the IUdR radiosensitization with the 60 keV photons from 241Am is about 1.5 times greater than that with 830 keV (average) photons from 226Ra. It was hypothesized that the enhanced IUdR radiosensitization for 60 keV photons was a result of a larger production of Auger electron cascades from the filling of K-shell vacancies in the iodine atoms, which have a K-shell binding energy of 33.2 keV. Since most of the photons from a 125I source have energies below 33.2 keV, it would be expected that IUdR radiosensitization with 28 keV (average) photons from 125I and 830 keV (average) photons from 226Ra would both be smaller than the radiosensitization with the 60 keV photons from 241Am. To test this hypothesis we compared IUdR radiosensitization for 226Ra, 241Am, and 125I at 0.72 Gy/hr, using Chinese hamster lung cells in vitro. The measured survival curves led to RBEs of 1.20 +/- 0.10 and 1.30 +/- 0.11 for 241Am and 125I photons relative to 226Ra; to IUdR radiosensitization factors at a 10(-5) M concentration of 1.35 +/- 0.11, 1.67 +/- 0.09, and 1.47 +/- 0.08 for 226Ra, 241Am, and 125I, respectively; and to radiosensitization factors at a 10(-4) M concentration of 1.89 +/- 0.16, 3.04 +/- 0.13, and 2.48 +/- 0.17 for 226Ra, 241Am, and 125I, respectively. These results indicate that IUdR produces significant radiosensitization with all three isotopes (226Ra, 241Am, and 125I) for continuous low dose rate irradiations at 0.72 Gy/hr. Also, we observed greater radiosensitization with 241Am photons compared to 226Ra on the higher energy side and to 125I on the lower energy side. These findings support the concept that photon-induced Auger electrons produce a significant increase in IUdR radiosensitization when photons with energies just above the K-edge of the iodine atom are employed for continuous low dose rate irradiations. These findings suggest that regimens combining IUdR infusion with temporary brachytherapy implants using low energy photons in relatively quiescent sites such as brain tumors may have clinical potential, and indicate the need for rigorous preclinical evaluation of this approach.

The toxicity of 5-thio-D-glucose (5TG) to mammalian cells in culture has been studied with respect to oxygen tension, concentration, and temperature. At 37 degrees C and at 5 mM concentration of the drug in normal growth medium, survival is 10(-3) for 4-hr exposure to 5 ppm O2; this increases to 0.5 for 24-hr exposure to 200 ppm O2. The relationship between survival and oxygen tension is nonlinear with the greatest change occurring between 50 and 100 ppm. The drug is essentially nontoxic to aerated cells. Drug toxicity increases with concentration up to about 5 mM at which point a plateau is reached. The effect of elevated temperature is to reduce the time required to obtain a specific level of survival, but temperatures as high as 42 degrees C had only a slight effect on drug toxicity for oxygen tensions higher than 100 ppm. The effect of D-glucose on the toxicity of 5TG was studied, and an inverse relationship was established. At D-glucose concentrations greater than 20 mM the toxicity of 5TG was nullified regardless of oxygen tension or 5TG concentration.

The effects of intense magnetic fields on the survival curves for aerated and hypoxic Chinese hamster lung cells exposed to 30 MV X-rays were investigated. A uniform 20-kilogauss magnetic field, as well as a non-uniform magnetic field with an average value of 17 . 5 kilogauss and a gradient of 2 . 3 kilogauss/cm, were employed. A study of the repair of sublethal damage for cells exposed to the magnetic field only during the split-dose irradiations, and the effect of exposure to the magnetic field alone for 2 hours, were also studied. For each of these four experiments, no effects attributable to the magnetic field were detected.

The survival of Chinese hamster cells exposed to 59.5 keV 241Am gamma rays was compared with that obtained after exposure to 226Ra gamma rays. The Fricke dosimeter in conjunction with the calculational techniques of transition-zone dosimetry was employed to determine the dose rates to the cells at the petri dish/growth medium interface. The dose rates to the cells ranged from 11 to 133 cGy/h. In all cases, cell survival versus dose was best described by a simple exponential function of dose. For both radiations, graphs of D0 versus dose rate show complex but similar patterns of peaks and valleys. As the curve for 241Am is displaced toward lower dose rates compared with that for 226Ra, the relative biological effectiveness of 241Am vs 226Ra varies considerably with dose rate, ranging from 1.7 at 20 cGy/h to 1.1 at 40 cGy/h to 1.6 at 50 cGy/h. This phenomenon may be due to the LET-dependent accumulation of cells at the G2 + M interface in the cell cycle. The mean unrestricted track-average LET of 241Am (3.7 keV/microns) is 12 times higher than that for 226Ra (0.31 keV/microns) but only one-fifth that of carbon ions (18 keV/microns) for which G2 + M pile-up is observed. Application of the in vitro data derived from this study to the clinical situation, where the dose rate decreases rapidly with distance from the source, suggests that, dose for dose, 241Am will produce results little different from those obtained with 226Ra.

The effect of the photon energy on the radiosensitization produced by iododeoxyuridine (IUdR) was examined using Chinese hamster cells in vitro. Radiosensitization by IUdR was considerably higher for 60 keV photons from 241Am sources than for the 860 keV photons (average energy) from 226Ra sources, under continuous low dose rate conditions applicable to intracavitary brachytherapy (a dose rate of 0.57 Gy/hr). Also, IUdR radiosensitization was higher for 250 kV X rays than for 4 MV X rays under the acute exposure conditions used in external beam radiation therapy (dose rates of 1 to 2 Gy/min). These data support the hypothesis that photons with energies just greater than 32.2 keV, the K-absorption edge of iodine, are more effective in causing cell damage than are photons of other energies, because their absorption results in the production of Auger electron cascades and therefore in the production of high linear energy transfer (LET) radiations.