Modelling of the oxygen enhancement ratio for ion beam radiation therapy

Wenzl, Tatiana; Wilkens, Jan J.

doi:10.1088/0031-9155/56/11/006

Cited by 113 publications

(159 citation statements)

References 94 publications

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“…AA8 cells were slightly more radiosensitive compared to CHO cells under both oxic and hypoxic conditions, nevertheless, we found that the OER values at the 10% survival level (D 10 or LD 90 ) were similar for both CHO cells (2.68 6 0.15) and AA8 cells (2.76 6 0.08) ( Table 1). The OER values of approximately 3 are in concordance with other published studies and suggest that our hypoxic conditions were close to anoxic conditions used in other studies (15)(16)(17)(18)(19).…”

Section: Calculation Of the Maximum Protection By Dmso (Dmso Method)supporting

confidence: 92%

OH Radicals from the Indirect Actions of X-Rays Induce Cell Lethality and Mediate the Majority of the Oxygen Enhancement Effect

Hirayama¹,

Ito

Noguchi

et al. 2013

Radiation Research

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We examined OH radical-mediated indirect actions from X irradiation on cell killing in wild-type Chinese hamster ovary cell lines (CHO and AA8) under oxic and hypoxic conditions, and compared the contribution of direct and indirect actions under both conditions. The contribution of indirect action on cell killing can be estimated from the maximum degree of protection by dimethylsulfoxide, which suppresses indirect action by quenching OH radicals without affecting the direct action of X rays on cell killing. The contributions of indirect action on cell killing of CHO cells were 76% and 50% under oxic and hypoxic conditions, respectively, and those for AA8 cells were 85% and 47%, respectively. Therefore, the indirect action on cell killing was enhanced by oxygen during X irradiation in both cell lines tested. Oxygen enhancement ratios (OERs) at the 10% survival level (D10 or LD90) for CHO and AA8 cells were 2.68 ± 0.15 and 2.76 ± 0.08, respectively. OERs were evaluated separately for indirect and direct actions, which gave the values of 3.75 and 2.01 for CHO, and 4.11 and 1.32 for AA8 cells, respectively. Thus the generally accepted OER value of ∼3 is best understood as the average of the OER values for both indirect and direct actions. These results imply that both indirect and direct actions on cell killing require oxygen for the majority of lethal DNA damage, however, oxygen plays a larger role in indirect than for direct effects. Conversely, the lethal damage induced by the direct action of X rays are less affected by oxygen concentration.

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Section: Calculation Of the Maximum Protection By Dmso (Dmso Method)supporting

confidence: 92%

OH Radicals from the Indirect Actions of X-Rays Induce Cell Lethality and Mediate the Majority of the Oxygen Enhancement Effect

Hirayama¹,

Ito

Noguchi

et al. 2013

Radiation Research

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“…It is estimated that indirect effects of free radicals account for approximately two-thirds of the DNA damage caused by X-rays [48]. For high LET radiation, classic studies performed by Barendsen et al and others have shown an inverse relationship between OER and LET where effect of oxygen on cell radiosensitivity becomes diminished (OER = 1.0) for LET greater than 140 keV/µm [21,85] (Figure 2B). The main hypothesis for the decrease of OER with increasing LET is that high LET radiation predominately causes direct DNA damage (estimated at about 75% for alpha particle of 150 keV/µm [86]) independent of the free radical inflicted indirect DNA damage, thereby less affected by oxygen.…”

Section: Effect Of Cell Cycle and Oxygenationmentioning

confidence: 97%

“…In a clinical trial of high LET carbon ion beam, Nakano et al compared its efficacy against hypoxic and normoxic cervical tumors and showed similar disease-free survival between hypoxic (<20 mmHg) and oxygenated (>20 mmHg) tumors suggesting that high LET radiation can overcome the radioresistance caused by tumor hypoxia [90]. Modeling analysis, however, suggest that the reduction of OER with high LET radiation under the clinical tumor hypoxic environment (0.5-20 mmHg) is relatively moderate with approximately 15% benefit over photon [85]. Furthermore, the findings that patients with hypoxic tumors are associated with poor prognosis with treatments independent of oxygen status (such as surgery) suggest that hypoxic tumor could have a malignant phenotype as a result of colony selection under hypoxic condition which in turn is maintained by its fast consumption of O 2 .…”

Section: Effect Of Cell Cycle and Oxygenationmentioning

confidence: 99%

Alpha Particle Emitter Radiolabeled Antibody for Metastatic Cancer: What Can We Learn from Heavy Ion Beam Radiobiology?

Song¹,

Senthamizhchelvan²,

Hobbs³

et al. 2012

Antibodies

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Alpha-particle emitter labeled monoclonal antibodies are being actively developed for treatment of metastatic cancer due to the high linear energy transfer (LET) and the resulting greater biological efficacy of alpha-emitters. Our knowledge of high LET particle radiobiology derives primarily from accelerated heavy ion beam studies. In heavy ion beam therapy of loco-regional tumors, the modulation of steep transition to very high LET peak as the particle approaches the end of its track (known as the Bragg peak) enables greater delivery of biologically potent radiation to the deep seated tumors while sparing normal tissues surrounding the tumor with the relatively low LET track segment part of the heavy ion beam. Moreover, fractionation of the heavy ion beam can further enhance the peak-to-plateau relative biological effectiveness (RBE) ratio. In contrast, internally delivered alpha particle radiopharmaceutical therapy lack the control of Bragg peak energy deposition and the dose rate is determined by the administered activity, alpha-emitter half-life and biological kinetics of the radiopharmaceutical. The therapeutic ratio of tumor to normal tissue is mainly achieved by tumor specific targeting of the carrier antibody. In this brief overview, we review the radiobiology of high LET radiations learned from ion beam studies and identify the features that are also applicable for the development of alpha-emitter labeled antibodies. The molecular mechanisms underlying DNA double strand break repair response to high LET radiation are also discussed.

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“…The surviving fraction SF (u) of each voxel is determined by the linear-quadratic model, which is an empirical formula for the predication of radiation response [14]:…”

Section: Sparse Dose Paintingmentioning

confidence: 99%

Sparse Dose Painting Based on a Dual-Pass Kinetic-Oxygen Mapping of Dynamic PET Images

Shi

Astner

Sun

et al. 2011

Lecture Notes in Computer Science

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Abstract. Development of molecular imaging such as positron-emission tomography (PET) offers an opportunity to optimize radiotherapy treatment planning by conforming the dose distribution to physiological details within tumors, so called dose painting. Quantification of the acquired images and an efficient and practical dose prescription remain two key questions in this field. This paper proposes a novel framework to optimize the dose prescription based on dual-pass modeling of dynamic [18 F]FMISO PET images. An optimization algorithm for sparse dose painting (SDP) is developed by minimizing a linear combination of two terms corresponding to the efficiency and total variation of the dose distribution with the constraint of a constant mean dose. Dose efficiency is defined using the linear-quadratic model. The radiosensitivity given by the oxygen tension is estimated using a dual-pass kinetic-oxygen mapping strategy. This is achieved by integrating a realistic [18 F]FMISO PET imaging simulation model, which can simulate the distribution of oxygen and tracer under the same tumor microenvironment setting. The algorithm was compared with a typical dose painting by number (DPBN) method in one data set of a patient with head and neck cancer.

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Modelling of the oxygen enhancement ratio for ion beam radiation therapy

Cited by 113 publications

References 94 publications

OH Radicals from the Indirect Actions of X-Rays Induce Cell Lethality and Mediate the Majority of the Oxygen Enhancement Effect

OH Radicals from the Indirect Actions of X-Rays Induce Cell Lethality and Mediate the Majority of the Oxygen Enhancement Effect

Alpha Particle Emitter Radiolabeled Antibody for Metastatic Cancer: What Can We Learn from Heavy Ion Beam Radiobiology?

Sparse Dose Painting Based on a Dual-Pass Kinetic-Oxygen Mapping of Dynamic PET Images

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