Rat testis as a radiobiological in vivo model for radionuclides.

The radiobiological effect of intracellularly localised radionuclides emitting low energy electrons (Auger electrons) has received much attention. Most in vivo studies reported have been performed in the mouse testis. We have investigated the rat testis as an in vivo radiobiological model, with sperm-head survival, testis weight loss and also alteration in the blood plasma hormone levels of FSH and LH as radiobiological endpoints. Validation of the rat testis model was evaluated by using mean absorbed doses of up to 10 Gy from intratesticularly (i.t.) injected (111)In oxine or local X-ray irradiation. Biokinetics of the i.t. injected radionuclide was analysed by scintillation camera imaging and used in the absorbed dose estimation. By the analysis of the autoradiographs, the activity distribution was revealed. Cell fractionation showed (111)In to be mainly associated with the cell nuclei. External irradiations were monitored by thermoluminescence dosimeters. The sperm-head survival was the most sensitive radiobiological parameter correlated to the mean absorbed dose, with a D(37) of 2.3 Gy for (111)In oxine and 1.3 Gy for X rays. The levels of plasma pituitary gonadal hormones FSH and LH were elevated for absorbed doses >7.7 Gy. This investigation shows that the radiobiological model based on the rat testis has several advantages compared with the previously commonly used mouse testis model. The model is appropriate for further investigations of basic phenomena such as radiation geometry, intracellular kinetics and heterogeneity, crucial for an understanding of the biological effect of low-energy electrons.

Dosimetry at 28 keV synchrotron radiation for cell irradiations.

Accurate dosimetry is a prerequisite for reliable comparisons between radiobiological irradiation experiments. Parameters affecting the determination of absorbed dose to cells in the shape of a small cell pellet in a centrifuge tube, irradiated by 28 keV mono-energetic photons from a synchrotron, were investigated. Thermoluminescent dosimeter (TLD), diode and ion chambers were utilized to monitor the irradiations. The distribution of the absorbed dose and such parameters as scatter, attenuation and interface dosimetry in the target, which influence the dose, were studied. A method for inter-calibrations of two different calibration sources by using TLD and TLD readers is given. Characteristics of the TLD, that is, fading, supralinearity, energy response, self-attenuation and mini-dosimetry were considered for the dosimetry. A method for correcting photon fluence attenuation in cylindrical TLDs is presented. The study shows that the absorbed dose to cells irradiated at low photon energy at a synchrotron irradiation facility can, using accurate dosimetry protocol, be correctly and reproducibly determined.

A model for evaluating therapeutic response of combined cancer treatment modalities: applied to treatment of subcutaneously implanted brain tumors (N32 and N29) in Fischer rats with pulsed electric fields (PEF) and 60Co-gamma radiation (RT).

The aim of the present study is to develop a mathematical model for evaluating therapeutic response of combined treatment modalities. The study was performed in rats of the Fischer-344 strain with rat glioma N32 or N29 tumors implanted subcutaneously on the thigh of the hind leg. Pulsed electric fields, PEF, with 16 exponentially decaying pulses with a maximum electric field strength of 140 V/mm and t(1/e)= 1 ms were first applied to the tumors. Then within 5 min radiation therapy with (60)Co-gamma radiation, RT, was given in daily fractions of 5 Gy. The animals were arranged into one group of controls and 3 groups of different kind of treatments: PEF only, RT only or combination of PEF + RT. At about 4 weeks after inoculation, the tumors were given the treatment sessions during one week. In 2 experimental series with totally 52 rats with N32 tumors, of which 16 were controls, were given 4 sessions of PEF treatments and RT (totally 20 Gy). In a special experimental series with totally 56 rats with N32 tumors, of which 10 were controls, the different groups were given 1, 2, 3 or 4 treatment sessions respectively. Another strain of glioma tumor, N29 with 62 tumors of which 14 were controls was studied in 2 series given 4PEF + 4RT and 2PEF + 4RT respectively. Fitting the data obtained from consecutive measurements of tumor volume (TV) of each individual tumor to an exponential model TV = TV(0). exp[TGR.t] estimated the tumor growth rate (TGR % per day) after the first day of treatment (t = 0). The TGR of N32 tumors treated with the combination of 4PEF + 4RT are significantly decreased compared to the controls (p < 0.0001), compared to RT alone (p < 0.0001) and compared to PEF alone (p < 0.001). The combined treatment of N32 gives significant effect on the tumor growth rate after 2, 3 and 4 treatment session while RT alone seems to be most efficient after one treatment of 5 Gy and PEF alone is most efficient after 2 treatments at 2 consecutive days. The TGR of N29 tumors treated with the combination of 4PEF + 4RT are significantly decreased compared to the controls (p < 0.05) but the combination of 2PEF + 4RT was more effective (p < 0.005). The specific therapeutic effect STE is defined as the difference between the average tumor growth rates of controls and exposed tumors divided by the average tumor growth rate of the controls. With 4PEF treatments alone the average STE value was 0.32 for N32 tumors and 0 for N29; for 4RT alone the STE values were 0.29 and 0.42 respectively, and for combined treatments 4PEF + 4RT 0.67 and 0.17 respectively. For the N29 tumors treated with 2PEF + 4RT the STE value was 0.53. The therapeutic enhancement ratio, TER, value increase with the number of treatment sessions and the TER of the combined treatments is above 1 in two of the N32 series, which indicates a synergistic effect of 4PEF + 4RT. This work demonstrate the use of our model for analyzing the combination PEF + RT, but it can also be used for evaluation the therapeutic effects of combining RT with chemotherapy or immunogenetic therapy.

Survival of mammalian cells exposed to ultrahigh dose rates from a laser-produced plasma x-ray source.

PURPOSE: To determine whether intense laser-produced x rays have an increased radiation hazard. MATERIALS AND METHODS: Mammalian cells were exposed to x rays from a laser-produced plasma that produced ultrahigh peak absorbed dose rates, up to a factor of 10(10) higher than those produced by conventional x rays used in imaging. The cell survival was studied as a function of the absorbed dose. The survival of mammalian cells exposed to high peak absorbed dose rates with laser-produced x rays was compared with the survival of cells exposed to standard absorbed dose rates with conventional x-ray sources. Comparative survival studies were performed by using a conventional x-ray tube and a cobalt 60 source. The absorbed doses in the irradiation field were measured with thermoluminescent dosimeters. RESULTS: Cell survival following irradiation by filtered, laser-produced x rays with a high dose rate was not markedly different from the survival following irradiation by conventional sources. There was, however, a notable difference between the survival after exposure to filtered, laser-produced x rays and the survival after exposure to unfiltered laser-produced x rays. CONCLUSION: Exposure to filtered, laser-produced x rays with a high dose rate does not lead to increased harm to mammalian cells exposed in vitro compared with the harm from exposure to x rays from conventional sources, which indicates that the use of high-power laser facilities for medical imaging is justified.

Cell survival after Auger electron emission from stable intracellular indium exposed to monochromatic synchrotron radiation.

The biological effect of Auger electrons emitted from indium in V79 cells was investigated. K-shell vacancies were induced by synchrotron x-rays. Two energies, 100 eV above and below the K-edge of indium, were used. The cell survival for controls was similar to that which has been reported by others, with D37 = 4.4 Gy. Indium-oxine-labelled cells exhibited a survival clearly below that of the controls, D37 = 3.2 Gy, but no significant difference in survival between irradiations above and below the K-edge could be observed. The explanation is, inter alia, that the number of photons interacting with indium atoms incorporated into the cell, is small compared with the number of photons interacting with other atoms in the cell. The toxicity of indium oxine made it impossible to incorporate a sufficient number of indium atoms into the cells to observe a difference in this study. However, monoenergetic irradiation above and below the K-edge, provides a technique for the investigation of basic biological effects of Auger processes.

Polymorphonuclear leucocyte sequestration in the lungs and liver following soft-tissue trauma: an in vivo study.

Neutrophils are thought to sequestrate in the lungs and the liver in association with shock. Indications for this have previously been demonstrated in different in vitro studies. In this experiment an in vivo technique for dynamic studies of pulmonary and liver neutrophil sequestration (PNT and LNT, respectively) is described. Autologous neutrophils from ten pigs were labelled with 111Indium-oxine. The pigs were placed under a scintillation camera for continuous recording of the activity distribution in the pigs during 105 minutes. Following a steady-state period of 15 minutes seven pigs were subjected to a standardized soft-tissue trauma. Three pigs were used as controls and not traumatized. Within 1-3 minutes after trauma the radioactivity over the lungs increased dramatically, indicating PNT. This was followed by a fast decrease but 90 minutes after trauma PNT levels were still significantly elevated. LNT showed a similar pattern, although the immediate increase was less dramatic. This study shows that PNT and LNT occur immediately after soft-tissue trauma and can be studied dynamically in vivo.