In vivo dosimetry in total body irradiation / Dosimetría in vivo en irradiación corporal total

Abstract Total Body Irradiation (TBI) is a radiotherapy technique that consists of irradiating homogeneously the whole patient's body and it is characterized by an extended source to surface distances and the use of large irradiation fields. The limitations of the available input data and inherent problems with the calculation procedures make it very difficult to accurately determine the dose distributions in TBI. For these reasons, it is highly recommended to use In Vivo Dosimetry (IVD), to guarantee the quality of TBI treatments as a direct measurement of the delivered dose. An IVD QA system was implemented based on semiconductor diodes and radiochromic films. For the commissioning of the system, both detector types were calibrated independently, using as reference an ionization chamber with a valid certificate in terms of absorbed dose to water (Dw). This guarantees the traceability of the measurements. An experiment was carried out to simulate a clinical TBI procedure to a phantom. In this way, the calibration of the dosimetry system was confirmed.

Resumen La irradiación total del cuerpo (TBI) es una técnica de radioterapia que consiste en irradiar de manera homogénea todo el cuerpo del paciente y se caracteriza por una fuente extendida a distancias superficiales y el uso de grandes campos de irradiación. Las limitaciones de los datos de entrada disponibles y los problemas inherentes con los procedimientos de cálculo hacen que sea muy difícil determinar con precisión las distribuciones de dosis en TBI. Por estos motivos, es altamente recomendable utilizar la dosimetría in vivo (IVD), para garantizar la calidad de los tratamientos de TBI como una medida directa de la dosis administrada. Se implementó un sistema IVD QA basado en diodos semiconductores y películas radiocromáticas. Para la puesta en marcha del sistema, ambos tipos de detectores se calibraron de forma independiente, utilizando como referencia una cámara de ionización con un certificado válido en términos de dosis absorbida en agua (Dw). Esto garantiza la trazabilidad de las mediciones. Se llevó a cabo un experimento para simular un procedimiento clínico de TBI a un fantasma. De esta forma, se confirmó la calibración del sistema de dosimetría.

Comparison of Total Body Irradiation (TBI) Conditioning with Non-TBI for Autologous Stem Cell Transplantation in Newly Diagnosed or Relapsed Mature T- and NK-Cell Non-Hodgkin Lymphoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This retrospective study was conducted for comparison of survival outcomes and toxicities of autologous stem cell transplantation (ASCT) based on the use of total body irradiation (TBI) as a part of the conditioning regimen in patients with mature T- and natural killer (NK)-cell lymphomas. MATERIALS AND METHODS: Patients who underwent ASCT in the upfront or salvage setting between January 2000 and December 2013 were analyzed. Patients were dichotomized according to the TBI group (n=38) and non-TBI group (n=60) based on the type of conditioning regimen for ASCT. RESULTS: Patients with responsive disease underwent upfront ASCT (TBI, n=16; non-TBI, n=29) whereas patients with refractory disease (TBI, n=9; non-TBI, n=12) or relapsed disease (TBI, n=13; non-TBI, n=19) underwent ASCT after salvage treatment. Hematologic and non-hematologic toxicities were manageable, and the median cumulative toxicity score according to Seattle criteria was estimated as 2 (range, 0 to 7) in both groups. No significant difference in 100-day mortality was observed between the TBI (13%, 5/38) and non-TBI (12%, 12/60) groups, and most deaths were related to disease progression. There was no difference in overall and progression-free survival; however, the TBI group showed a trend of better survival in upfront and salvage ASCT than the non-TBI group. However, patients with refractory disease showed the worst outcome regardless of the use of TBI. Patients who showed complete response before ASCT showed better progression-free survival than thosewho showed partial response. CONCLUSION: TBI could be used as an effective part of conditioning for ASCT in patients with mature T- and NK-cell lymphomas.

Effects of Whole Body Irradiation on Morphine, DAMGO, DPDPE, U50,488H and beta-endorphin-Induced Antinociception

Opioid receptors have been pharmacologically classified as micro, delta, kappa and epsilon. We have recently reported that the antinociceptive effect of morphine (a micro-opioid receptor agonist), but not that of beta-endorphin (a novel micro/epsilon-opioid receptor agonist), is attenuated by whole body irradiation (WBI). It is unclear at present whether WBI has differential effects on the antinociceptive effects of micro-, delta-, kappa- and epsilon-opioid receptor agonists. In our current experiments, male ICR mice were exposed to WBI (5Gy) from a 60Co gamma-source and the antinociceptive effects of opioid receptor agonists were assessed two hours later using the hot water (52degrees C) tail-immersion test. Morphine and D-Ala2,N-Me-Phe4,Gly-olenkephalin(DAMGO), [D-Pen2-D-Pen5]enkephalin (DPDPE), trans-3,4-Dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzeneacetamide (U50,488H), and beta-endorphin were tested as agonists for micro, delta, kappa, and epsilon-opioid receptors, respectively. WBI significantly attenuated the antinociceptive effects of morphine and DAMGO, but increased those of beta-endorphin. The antinociceptive effects of DPDPE and U50,488H were not affected by WBI. In addition, to more preciously understand the differential effects of WBI on micro- and epsilon-opioid receptor agonists, we assessed pretreatment effects of beta-funaltrexamine (beta-FNA, a micro-opioid receptor antagonist) or beta-endorphin1-27 (beta-EP1-27, an epsilon-opioid receptor antagonist), and found that pretreatment with beta-FNA significantly attenuated the antinociceptive effects of morphine and beta-endorphin by WBI. beta-EP1-27 significantly reversed the attenuation of morphine by WBI and significantly attenuated the increased effects of beta-endorphin by WBI. The results demonstrate differential sensitivities of opioid receptors to WBI, especially for micro- and epsilon-opioid receptors.

Total body γ-irradiation decreases wound breaking strength during wound healing in rats / 第二军医大学学报

Objective: To investigate the influence of total body irradiation with different doses of 60Coγ on wound breaking strength during wound healing in rats. Methods: Rats were exposed to 60Coγ radiation at dosages of 4,6 ,and 8 Gy. Within 30 min after irradiation, full thickness skin wounds were made on the shaved back of rats to establish animal models of irradiated-trauma injury plus skin wounds (n=20), and non-irradiated rats with pure incision injury were used as controls (n=10). The rats were sacrificed at day 10 after treatment, and the full thickness skin wounds were harvested. Bio-mechanics method and histopathology examination were used to evaluate the wound breaking strength and histological features after healing. Results: The wound breaking strength of model groups were greatly retarded with the increase of irradiation doses. Statistical results showed that on day 10 the wound breaking strength values were significantly different between 4 Gy group ([114.26±0.29] g) and control group ([117.12±1.86] g, P>0.05), and the wound breaking strength values of 6 Gy group ([91.87±1.96] g) and 8 Gy group ([55.26±2.64] g) were significantly lower than that of the control group (P<0.05). H-E staining showed that the wounds in the irradiation trauma groups had looser and disorder collagenous fiber and less fibroblast proliferation than control group. Conclusion: Radiation injury may result in delayed wound healing, and the wound breaking strength decreases with the increase of irradiation dose in model of irradiation injury plus full thickness skin wounds.

A Follow-up for Myasthenia Gravis after Low Dose Whole Body Irradiation

BACKGROUND: Whole body irradiation (WBI) for myasthenia gravis is known to produce prolonged immunosuppres-sion with rare side effects. This study evaluated the duration of immunosuppression effects of WBI for long-term fol-low-up and decision time of 'booster' WBI treatments by analyzing clinical symptoms and laboratory findings. METHODS: We studied 11 patients with intractable myasthenia gravis. All patients had been treated with WBI and were followed for at least 5 years except for 2 patients died. Clinical status and immunological parameters were assessed at baseline and every year after the initial dose of irradiation. During the follow-up period, patients with declining clinical or immunological parameters were given 'booster' WBI treatments. RESULTS: WBI was associated with objective clini-cal improvements in seven patients: 3 patients had none or mild symptoms without any medications, 3 patients had 'booster' WBI treatments at 34 months(25-40 months) due to clinical or immunological declines, 1 patient had a stable clinical course with anticholinesterase medication. WBI was associated with clinical decline or no change in four patients: 2 patients died and 2 patients did not experience a change in clinical status. WBI produced a long-lasting lym-phopenia for more than 2 years with decreased absolute lymphocytes counts. There was no statistical differences in clinical and immunological parameters between the 'booster' WBI groups and non-'booster' WBI groups in good responders. 'Booster' WBI patients had no significant side effects. CONCLUSIONS: WBI has an effective therapeutic modality in intractable long-term myasthenia gravis. In this study, the duration of immnunosuppression effects of WBI was found to last 2 years. It is suggested that patients with declining clinical or immunological parameters be given 'booster' WBI treatments.

Alteration of Phospholipase D Activity in the Rat Tissues by Irradiation / 대한치료방사선과학회지

PURPOSE: Phospholipase D (PLD) catalyzes the hydrolysis of phosphatidyl choline to phosphatidic acid (PA) and choline. Recently, PLD has been drawing much attentions and considered to be associated with cancer process since it is involved in cellular signal transduction. In this experiment, oleate-PLD activities were measured in various tissues of the living rats after whole body irradiation. MATERIAL AND METHODS: The reaction mixture for the PLD assay contained 0.1microCi 1,2-di[1-14C]palmitoyl phosphatidylcholine, 0.5mM phosphatidylcholine, 5mM sodium oleate, 0.2% taurodeoxycholate, 50mM HEPES buffer (pH 6.5), 10mM CaCl2, and 25mM KF. phosphatidic acid, the reaction product, was separated by TLC and its radioactivity was measured with a scintillation counter. The whole body irradiation was given to the female Wistar rats via Cobalt 60 Teletherapy with field size of 10cm x 10cm and an exposure of 2.7Gy per minute to the total doses of 10Gy and 25Gy. RESULTS: Among the tissues examined, PLD activity in lung was the highest one and was followed by kidney, skeletal muscle, brain, spleen, bone marrow, thymus, and liver. Upon irradiation, alteration of PLD activity was observed in thymus, spleen, lung, and bone marrow. Especially PLD activities of the spleen and thymus revealed the highest sensitivity toward gamma-ray with more than two times amplification in their activities. In contrast, the PLD activity of bone marrow appears to be reduced to nearly 30%. Irradiation effect was hardly detected in liver which showed the lowest PLD activity. CONCLUSION: The PLD activities affected most sensitively by the whole-body irradiation seem to be associated with organs involved in immunity and hematopoiesis. This observation strongly indicates that the PLD is closely related to the physiological function of these organs. Furthermore, radiation stress could offer an important means to explore the phenomena covering from cell proliferation to cell death on these organs.

Study of sodium homeostasis in blood in whole body gamma- irradiated rats.

Adult male rats were subjected to whole body irradiation of 400 and 1000 rads and sodium homeostasis in blood was studied on the 1st, 4th and 7th days after exposure. A significant decrease in red cell adenosine triphosphatase, progressive loss of erythrocytic potassium and alteration in influx and efflux of sodium 22 in red cells in vitro were observed in these rats.