Paul Bongiorni

Measurement of dose-rate constant for 103Pd seeds with air kerma strength calibration based upon a primary national standard

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 manufacturers 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.

Iododeoxyuridine radiosensitization by low- and high-energy photons for brachytherapy dose rates

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.

Enhancement of iudr radiosensitization by low energy photons

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.

Dose rate constant of a cesium-131 interstitial brachytherapy seed measured by thermoluminescent dosimetry and gamma-ray spectrometry.

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.

Response of mammalian cells irradiated with 30 MV X-rays in the presence of a uniform 20-kilogauss magnetic field

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.

Visible-Light and X Irradiations of Chinese Hamster Lung Cells Treated with Hematoporphyrin Derivative

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.

Enhanced IUdR radiosensitization by 241Am photons relative to 226Ra and 125I photons at 0.72 Gy/hr

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.

Relative Biological Effectiveness of 103Pd and 125I Photons for Continuous Low-Dose-Rate Irradiation of Chinese Hamster Cells

Abstract Nath, R., Bongiorni, P., Chen, Z., Gragnano, J. and Rockwell, S. Relative Biological Effectiveness of 103Pd and 125I Photons for Continuous Low-Dose-Rate Irradiation of Chinese Hamster Cells. Radiat. Res. 163, 501–509 (2005). Monolayers of Chinese hamster lung cells (CCL-16) in a polystyrene phantom were irradiated in vitro by 103Pd and 125I sources at dose rates of 6 to 72 cGy/h. Cell survival curves for acute high-dose-rate irradiation (over 30 Gy/h) were also measured using nearly monoenergetic X-ray beams which were designed to simulate the mean energies of photons emitted by 125I and 103Pd and also using a clinical 250 kVp X-ray beam. A profound dose-rate effect is observed over the dose-rate range of 6 to 20 cGy/h. An inverse dose-rate effect was observed for both radionuclides, with its onset occurring at a dose rate of about 20–30 cGy/h. The average RBE of 103Pd relative to 125I was determined to be 1.45 ± 0.07, 1.41 ± 0.07, 0.70 ± 0.07 and 1.49 ± 0.07 at dose rates of 6.9, 12.6, 19.0 and 26.7 cGy/h, respectively. Because 103Pd implants are generally prescribed at a higher initial dose rate (21 cGy/h) than the corresponding 125I implants (7 cGy/h), the effects of both dose rate and photon energy on biological response must be considered together. For the CCL-16 cells, the RBE of 103Pd at 19.0 cGy/h relative to that of 125I at 6.9 cGy/h was estimated to be 2.3 ± 0.5.

On the Specific Toxicity of 5-Thio-D-glucose to Hypoxic Cells

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.

Dose rate dependence of the relative biological effectiveness of 103Pd for continuous low dose rate irradiation of BA1112 rhabdomyosarcoma cells in vitro relative to acute exposures

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 103Pd 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.