A quantitative description of the compatibility of technetium-selective chromatographic technetium-99m separation with low specific activity molybdenum-99.

Technetium-99m generators employing a technetium-selective stationary phase are a chromatographic instrument developed for use with Mo having low specific activity (LSA); particularly, Mo produced by electron accelerators. This paper presents a mathematical description of technetium-selective chromatographic (TSC) Tc separation and analyzes its compatibility with LSA Mo. We developed a theoretical formula for TSC Tc separation by discretizing its pertechnetate selectivity, and validated it using an electron linear accelerator and activated carbon-based TSC (AC-TSC) Tc generators.

Laser-driven multi-MeV high-purity proton acceleration via anisotropic ambipolar expansion of micron-scale hydrogen clusters.

Multi-MeV high-purity proton acceleration by using a hydrogen cluster target irradiated with repetitive, relativistic intensity laser pulses has been demonstrated. Statistical analysis of hundreds of data sets highlights the existence of markedly high energy protons produced from the laser-irradiated clusters with micron-scale diameters. The spatial distribution of the accelerated protons is found to be anisotropic, where the higher energy protons are preferentially accelerated along the laser propagation direction due to the relativistic effect.

Prediction of the position of external markers using a recurrent neural network trained with unbiased online recurrent optimization for safe lung cancer radiotherapy.

Background And Objective: During lung cancer radiotherapy, the position of infrared reflective objects on the chest can be recorded to estimate the tumor location. However, radiotherapy systems have a latency inherent to robot control limitations that impedes the radiation delivery precision. Prediction with online learning of recurrent neural networks (RNN) allows for adaptation to non-stationary respiratory signals, but classical methods such as real-time recurrent learning (RTRL) and truncated backpropagation through time are respectively slow and biased.

A preliminary biodistribution study of [Tc]sodium pertechnetate prepared from an electron linear accelerator and activated carbon-based Tc generator.

Introduction: Production of Mo/Tc using an electron linear accelerator (linac) and activated carbon (AC)-based Tc generator (linac-AC) is an alternative approach to the conventional fission production of Mo/Tc. As a preliminary investigation of the clinical applicability of a linac-AC-derived Tc radiopharmaceutical, the biodistribution of linac-AC-derived [Tc]sodium pertechnetate ([Tc]NaTcO) was measured and compared against fission-derived [Tc]NaTcO at one time point.

Methods: Mo was produced by irradiating nonenriched MoO targets with bremsstrahlung photons generated from 55.

Prediction of the motion of chest internal points using a recurrent neural network trained with real-time recurrent learning for latency compensation in lung cancer radiotherapy.

During the radiotherapy treatment of patients with lung cancer, the radiation delivered to healthy tissue around the tumor needs to be minimized, which is difficult because of respiratory motion and the latency of linear accelerator (LINAC) systems. In the proposed study, we first use the Lucas-Kanade pyramidal optical flow algorithm to perform deformable image registration (DIR) of chest computed tomography (CT) scan images of four patients with lung cancer. We then track three internal points close to the lung tumor based on the previously computed deformation field and predict their position with a recurrent neural network (RNN) trained using real-time recurrent learning (RTRL) and gradient clipping.

Development of a markerless tumor-tracking algorithm using prior four-dimensional cone-beam computed tomography.

Respiratory motion management is a huge challenge in radiation therapy. Respiratory motion induces temporal anatomic changes that distort the tumor volume and its position. In this study, a markerless tumor-tracking algorithm was investigated by performing phase recognition during stereotactic body radiation therapy (SBRT) using four-dimensional cone-beam computer tomography (4D-CBCT) obtained at patient registration, and in-treatment cone-beam projection images.

DNA Repair Deficient Chinese Hamster Ovary Cells Exhibiting Differential Sensitivity to Charged Particle Radiation under Aerobic and Hypoxic Conditions.

It has been well established that hypoxia significantly increases both cellular and tumor resistance to ionizing radiation. Hypoxia associated radiation resistance has been known for some time but there has been limited success in sensitizing cells to radiation under hypoxic conditions. These studies show that, when irradiated with low linear energy transfer (LET) gamma-rays, poly (ADP-ribose), polymerase (PARP), Fanconi Anemia (FANC), and mutant Chinese Hamster Ovary (CHO) cells respond similarly to the non-homologous end joining (NHEJ) and the homologous recombination (HR) repair mutant CHO cells.

Design and evaluation of a novel flavonoid-based radioprotective agent utilizing monoglucosyl rutin.

In this study, three novel flavonoid composite materials, created by combining an aglycone [quercetin (QUE), hesperetin (HES) or naringenin (NAR)] with monoglucosyl rutin (MGR), were designed to test for improved radioprotectivity compared with that provided by administration of MGR alone. Aglycone in the MGR-composite state was highly soluble in water, compared with aglycone alone dissolved in dimethyl sulfoxide or distilled water. The antioxidant activity of the three flavonoid composites was as high as that of MGR only.

Improved proton CT imaging using a bismuth germanium oxide scintillator.

Range uncertainty is among the most formidable challenges associated with the treatment planning of proton therapy. Proton imaging, which includes proton radiography and proton computed tomography (pCT), is a useful verification tool. We have developed a pCT detection system that uses a thick bismuth germanium oxide (BGO) scintillator and a CCD camera.

Oxygen Enhancement Ratio in Radiation-Induced Initial DSBs by an Optimized Flow Cytometry-based Gamma-H2AX Analysis in A549 Human Cancer Cells.

High-linear energy transfer (LET) heavy ions cause higher therapeutic effects than low-LET radiation due to lower dependency on oxygen concentration in tumor cell killing. The lethality after irradiation largely depends on DNA double-strand breaks (DSBs), however the detailed LET dependency for DSB induction under oxic and hypoxic conditions has not been reported. Therefore, we evaluated the oxygen enhancement ratio (OER) of heavy ion-induced DSB induction using a highly-optimized flow cytometry-based method of γ-H2AX detection.

Investigation of the relative biological effectiveness and uniform isobiological killing effects of irradiation with a clinical carbon SOBP beam on DNA repair deficient CHO cells.

Spread-out Bragg peak (SOBP) C ions have been used clinically in charged particle radiation therapy for years. An SOBP beam consists of various monoenergetic Bragg peaks; however, the biological effect of irradiation with an SOBP beam track has not been well-studied. In order to determine the clinically prospective molecular targets, radiosensitivity to the beam track in DNA repair deficient cell lines was investigated.

In vitro screening of radioprotective properties in the novel glucosylated flavonoids.

Novel glucosyl flavonoids are developed by the addition of glucose to naturally occurring flavonoids. Flavonoids are known antioxidants that possess radioprotective properties. In order to investigate the radioprotective properties of novel glucosyl flavonoids, in vitro DNA double-strand breaks (DSBs) analysis was carried out.

Nontoxic concentration of DNA-PK inhibitor NU7441 radio-sensitizes lung tumor cells with little effect on double strand break repair.

High-linear energy transfer (LET) heavy ions have been increasingly employed as a useful alternative to conventional photon radiotherapy. As recent studies suggested that high LET radiation mainly affects the nonhomologous end-joining (NHEJ) pathway of DNA double strand break (DSB) repair, we further investigated this concept by evaluating the combined effect of an NHEJ inhibitor (NU7441) at a non-toxic concentration and carbon ions. NU7441-treated non-small cell lung cancer (NSCLC) A549 and H1299 cells were irradiated with X-rays and carbon ions (290 MeV/n, 50 keV/μm).

Development of proton CT imaging system using plastic scintillator and CCD camera.

A proton computed tomography (pCT) imaging system was constructed for evaluation of the error of an x-ray CT (xCT)-to-WEL (water-equivalent length) conversion in treatment planning for proton therapy. In this system, the scintillation light integrated along the beam direction is obtained by photography using the CCD camera, which enables fast and easy data acquisition. The light intensity is converted to the range of the proton beam using a light-to-range conversion table made beforehand, and a pCT image is reconstructed.

Data for induction of cytotoxic response by natural and novel quercetin glycosides.

The flavonoids quercetin, and its natural glycosides isoquercetin and rutin, are phytochemicals commonly consumed in plant-derived foods and used as a food beverage additive. Semi-synthetic maltooligosyl isoquercetin, monoglucosyl rutin and maltooligosyl rutin were developed by synthetic glycosylation to improve their water solubility for food and other applications. Using a system of Chinese hamster ovary (CHO) cells, this study examined the differences in cytotoxic responses induced by short and continuous exposure of natural and synthetic flavonoids.

Hyperthermia-induced radiosensitization in CHO wild-type, NHEJ repair mutant and HR repair mutant following proton and carbon-ion exposure.

The DNA repair mechanisms involved in hyperthermia-induced radiosensitization with proton and carbon ion radiation exposure were investigated in the present study. In a previous study, Chinese hamster ovary (CHO) cells were exposed to low linear energy transfer (LET) photon radiation. These cells can be sensitized by hyperthermia as a result of inhibition of homologous recombination (HR) repair.

Solution Radioactivated by Hadron Radiation Can Increase Sister Chromatid Exchanges.

When energetic particles irradiate matter, it becomes activated by nuclear reactions. Radioactivation induced cellular effects are not clearly understood, but it could be a part of bystander effects. This investigation is aimed at understanding the biological effects from radioactivation in solution induced by hadron radiation.

VE-821, an ATR inhibitor, causes radiosensitization in human tumor cells irradiated with high LET radiation.

Background: High linear energy transfer (LET) radiation such as carbon ion particles is successfully used for treatment of solid tumors. The reason why high LET radiation accomplishes greater tumor-killing than X-rays is still not completely understood. One factor would be the clustered or complex-type DNA damages.

Induction of cytotoxic and genotoxic responses by natural and novel quercetin glycosides.

The flavonoids quercetin, and its natural glycosides isoquercetin and rutin, are phytochemicals commonly consumed in plant-derived foods. Semi-synthetic water-soluble isoquercetin and rutin glycosides, maltooligosyl isoquercetin, monoglucosyl rutin and maltooligosyl rutin were developed by synthetic glycosylation to overcome solubility challenges for improved incorporation in food and medicinal applications. Quercetin and its natural glycosides are known to induce genetic instability and decrease cell proliferation.

Novel characteristics of CtIP at damage-induced foci following the initiation of DNA end resection.

Homologous recombination (HR) is a major repair pathway for DNA double strand breaks (DSBs), and end resection, which generates a 3'-single strand DNA tail at the DSB, is an early step in the process. Resection is initiated by the Mre11 nuclease together with CtIP. Here, we describe novel characteristics of CtIP at DSBs.

Monoglucosyl-rutin as a potential radioprotector in mammalian cells.

In the present study, the role of monoglucosyl‑rutin as a potential radioprotector was investigated using mammalian cell culture models. Cell survival and DNA damage were assessed using colony formation, sister chromatid exchange and γH2AX assays. It was demonstrated that monoglucosyl‑rutin was able to increase cell survival when exposed to ionizing radiation, possibly by decreasing the amount of base damage experienced by the cell.

Natural and glucosyl flavonoids inhibit poly(ADP-ribose) polymerase activity and induce synthetic lethality in BRCA mutant cells.

Poly(ADP-ribose) polymerase (PARP) inhibitors have been proven to represent superior clinical agents targeting DNA repair mechanisms in cancer therapy. We investigated PARP inhibitory effects of the natural and synthetic flavonoids (quercetin, rutin, monoglucosyl rutin and maltooligosyl rutin) and tested the synthetic lethality in BRCA2 mutated cells. In vitro ELISA assay suggested that the flavonoids have inhibitory effects on PARP activity, but glucosyl modifications reduced the inhibitory effect.

Comparison of human chordoma cell-kill for 290 MeV/n carbon ions versus 70 MeV protons in vitro.

Background: While the pace of commissioning of new charged particle radiation therapy facilities is accelerating worldwide, biological data pertaining to chordomas, theoretically and clinically optimally suited targets for particle radiotherapy, are still lacking. In spite of the numerous clinical reports of successful treatment of these malignancies with this modality, the characterization of this malignancy remains hampered by its characteristic slow cell growth, particularly in vitro.

Methods: Cellular lethality of U-CH1-N cells in response to different qualities of radiation was compared with immediate plating after radiation or as previously reported using the multilayered OptiCell™ system.

A study of internal defect testing with the laser-EMAT ultrasonic method.

This paper studies the ultrasonic detection and evaluation of internal volume defects in metals using laser generation and electromagnetic acoustic transducer (EMAT) detection. A finite element model is developed to simulate the interaction of laser-generated ultrasonic waves with the defect in the material. Not only have the directly scattered shear waves been observed, but also the mode-converted creeping waves on the defect surface.