Demonstration of event position reconstruction based on diffusion in the NEXT-white detector.

Noble element time projection chambers are a leading technology for rare event detection in physics, such as for dark matter and neutrinoless double beta decay searches. Time projection chambers typically assign event position in the drift direction using the relative timing of prompt scintillation and delayed charge collection signals, allowing for reconstruction of an absolute position in the drift direction. In this paper, alternate methods for assigning event drift distance via quantification of electron diffusion in a pure high pressure xenon gas time projection chamber are explored. Data from the NEXT-White detector demonstrate the ability to achieve good position assignment accuracy for both high- and low-energy events. Using point-like energy deposits from 83mKr calibration electron captures (E∼45 keV), the position of origin of low-energy events is determined to 2 cm precision with bias <1mm. A convolutional neural network approach is then used to quantify diffusion for longer tracks (E≥1.5 MeV), from radiogenic electrons, yielding a precision of 3 cm on the event barycenter. The precision achieved with these methods indicates the feasibility energy calibrations of better than 1% FWHM at Qßß in pure xenon, as well as the potential for event fiducialization in large future detectors using an alternate method that does not rely on primary scintillation.

Characterization of a 4παß(LS)-γ(HPGe) prototype system for low-background measurements.

A ground-level prototype system for low-background measurements was developed and tested. The system consists of a high-purity germanium (HPGe) detector used for detecting γ rays and coupled to a liquid scintillator (LS) used for detecting α and ß particles. Both detectors are surrounded by shielding materials and anti-cosmic detectors ("veto") used to suppress background events. The energy and timestamp of detected α, ß and γ emissions are recorded event-by-event and analyzed offline. By requiring timing coincidence between the HPGe and LS detectors, background events originating from outside the volume of the measured sample can be effectively rejected. The system performance was evaluated using liquid samples containing known activities of an α emitter (241Am) or a ß emitter (60Co) whose decays are accompanied by γ rays. The LS detector was found to provide a solid angle of almost 4π for α and ß particles. Compared to the traditional γ-singles mode, operating the system in coincidence mode (i.e., α-γ or ß-γ) reduced the background counts by a factor of ∼100. Consequently, the minimal detectable activity for 241Am and 60Co was improved by a factor of 9, being 4 mBq and 1 mBq for an 11-d measurement, respectively. Furthermore, by applying a spectrometric cut in the LS spectrum that corresponds to α emission from 241Am, a background reduction factor of ∼2400 (compared to γ-singles mode) was achieved. Beyond low-background measurements, this prototype exhibits additional compelling features, such as the ability to focus on certain decay channels and study their properties. This concept for a measurement system may be of interest to laboratories that monitor environmental radioactivity, studies involving environmental measurements and/or trace-level radioactivity.

Evaluating the intensity of the 'prompt' 140.5 keV γ-ray of 99Mo using a 4παß(LS)-γ(HPGe) measurement system.

The absolute intensity for the 'prompt' 140.5 keV gamma-ray of 99Mo was evaluated using the ß-γ coincidence technique. A liquid sample of 99Mo was prepared from a99Mo/99mTc generator and measured in a 4παß(LS)-γ(HPGe) system that comprises a Liquid Scintillator (LS) detector and a High-Purity Germanium (HPGe) detector. The sample was introduced into scintillation fluid embedded in a photo-reflector assembly that provides almost 100% efficiency for detecting ß particles (in the energy range of intreset). The combination of the HPGe and the LS detectors provided a highly effective rejection mechanism for non-coincident events. Thereby, the distinction between the detected 140.5 keV events originating from decays of 99mTc (IT) and those from transitions bypassing the metastable state could be obtained and the 'prompt' intensity was evaluated directly. The system was calibrated for detecting ß particles and γ-rays using radioactive sources of known activities and having identical geometry as the sample containing 99Mo. The absolute intensity of the 'prompt' 140.5 keV was found to be (5.21 ± 0.02stat±0.16sys)%, in good agreement with results from more recently reported works.

Initial Safety and Tumor Control Results From a "First-in-Human" Multicenter Prospective Trial Evaluating a Novel Alpha-Emitting Radionuclide for the Treatment of Locally Advanced Recurrent Squamous Cell Carcinomas of the Skin and Head and Neck.

PURPOSE: Our purpose was to report the feasibility and safety of diffusing alpha-emitter radiation therapy (DaRT), which entails the interstitial implantation of a novel alpha-emitting brachytherapy source, for the treatment of locally advanced and recurrent squamous cancers of the skin and head and neck. METHODS AND MATERIALS: This prospective first-in-human, multicenter clinical study evaluated 31 lesions in 28 patients. The primary objective was to determine the feasibility and safety of this approach, and the secondary objectives were to evaluate the initial tumor response and local progression-free survival. Eligibility criteria included all patients with biopsy-proven squamous cancers of the skin and head and neck with either primary tumors or recurrent/previously treated disease by either surgery or prior external beam radiation therapy; 13 of 31 lesions (42%) had received prior radiation therapy. Toxicity was evaluated according to the Common Terminology Criteria for Adverse Events version 4.03. Tumor response was assessed at 30 to 45 days at a follow-up visit using the Response Evaluation Criteria in Solid Tumors, version 1.1. Median follow-up time was 6.7 months. RESULTS: Acute toxicity included mostly local pain and erythema at the implantation site followed by swelling and mild skin ulceration. For pain and grade 2 skin ulcerations, 90% of patients had resolution within 3 to 5 weeks. Complete response to the Ra-224 DaRT treatment was observed in 22 lesions (22/28; 78.6%); 6 lesions (6/28, 21.4%) manifested a partial response (>30% tumor reduction). Among the 22 lesions with a complete response, 5 (22%) developed a subsequent local relapse at the site of DaRT implantation at a median time of 4.9 months (range, 2.43-5.52 months). The 1-year local progression-free survival probability at the implanted site was 44% overall (confidence interval [CI], 20.3%-64.3%) and 60% (95% CI, 28.61%-81.35%) for complete responders. Overall survival rates at 12 months post-DaRT implantation were 75% (95% CI, 46.14%-89.99%) among all patients and 93% (95% CI, 59.08%-98.96%) among complete responders. CONCLUSIONS: Alpha-emitter brachytherapy using DaRT achieved significant tumor responses without grade 3 or higher toxicities observed. Longer follow-up observations and larger studies are underway to validate these findings.

Search for Event Rate Modulation in XENON100 Electronic Recoil Data.

We have searched for periodic variations of the electronic recoil event rate in the (2-6) keV energy range recorded between February 2011 and March 2012 with the XENON100 detector, adding up to 224.6 live days in total. Following a detailed study to establish the stability of the detector and its background contributions during this run, we performed an unbinned profile likelihood analysis to identify any periodicity up to 500 days. We find a global significance of less than 1σ for all periods, suggesting no statistically significant modulation in the data. While the local significance for an annual modulation is 2.8σ, the analysis of a multiple-scatter control sample and the phase of the modulation disfavor a dark matter interpretation. The DAMA/LIBRA annual modulation interpreted as a dark matter signature with axial-vector coupling of weakly interacting massive particles to electrons is excluded at 4.8σ.

Comparative in vitro microdosimetric study of murine- and human-derived cancer cells exposed to alpha particles.

Diffusing alpha-emitter radiation therapy (DaRT) is a proposed new form of brachytherapy using α particles to treat solid tumors. The method relies on implantable ²²4Ra-loaded sources that continually release short-lived α-particle-emitting atoms that spread inside the tumor over a few millimeters. This treatment was demonstrated to have a significant effect on tumor growth in murine and human-derived models, but the degree of tumor response varied across cell lines. Tumor response was found to correlate with the degree of radionuclide spread inside the tumor. In this work we examined the radiosensitivity of individual cells to determine its relationship to tumor response. Cells were irradiated in vitro by α particles using a ²²8Th irradiator, with the mean lethal dose, D0, estimated from survival curves generated by standard methods. The results were further analyzed by microdosimetric tools to calculate z0, the specific energy resulting in a survival probability of 1/e for a single cell, which is considered to better represent the intrinsic radiosensitivity of individual cells. The results of the study demonstrate that, as a rule, tumors that respond more favorably to the DaRT treatment are also characterized by higher intrinsic cellular radiosensitivities, with D0 ranging from 0.7 Gy to 1.5 Gy for the extreme cases and z0 following the same trend.

The treatment of solid tumors by alpha emitters released from (224)Ra-loaded sources-internal dosimetry analysis.

Diffusing alpha-emitters radiation therapy (DART) is a proposed new form of brachytherapy, allowing the treatment of solid tumors by alpha particles. DART utilizes implantable sources carrying small activities of radium-224, which continually release into the tumor radon-220, polonium-216 and lead-212 atoms, while radium-224 itself remains fixed to the source. The released atoms disperse inside the tumor by diffusive and convective processes, creating, through their alpha emissions, a high-dose region measuring several mm in diameter about each source. The efficacy of DART has been demonstrated in preclinical studies on mice-borne squamous cell carcinoma and lung tumors and the method is now being developed toward clinical trials. This work studies DART safety with respect to the dose delivered to distant organs as a result of lead-212 leakage from the tumor through the blood, relying on a biokinetic calculation coupled to internal dose assessments. It is found that the dose-limiting organs are the kidneys and red bone marrow. Assuming a typical source spacing of approximately 5 mm and a typical radium-224 activity density of 0.4-0.8 MBq g(-1) of tumor tissue, it is predicted that tumors weighing up to several hundred grams may be treated without reaching the tolerance dose in any organ.

Treatment of solid tumors by interstitial release of recoiling short-lived alpha emitters.

A new method utilizing alpha particles to treat solid tumors is presented. Tumors are treated with interstitial radioactive sources which continually release short-lived alpha emitting atoms from their surface. The atoms disperse inside the tumor, delivering a high dose through their alpha decays. We implement this scheme using thin wire sources impregnated with (224)Ra, which release by recoil (220)Rn, (216)Po and (212)Pb atoms. This work aims to demonstrate the feasibility of our method by measuring the activity patterns of the released radionuclides in experimental tumors. Sources carrying (224)Ra activities in the range 10-130 kBq were used in experiments on murine squamous cell carcinoma tumors. These included gamma spectroscopy of the dissected tumors and major organs, Fuji-plate autoradiography of histological tumor sections and tissue damage detection by Hematoxylin-Eosin staining. The measurements focused on (212)Pb and (212)Bi. The (220)Rn/(216)Po distribution was treated theoretically using a simple diffusion model. A simplified scheme was used to convert measured (212)Pb activities to absorbed dose estimates. Both physical and histological measurements confirmed the formation of a 5-7 mm diameter necrotic region receiving a therapeutic alpha-particle dose around the source. The necrotic regions shape closely corresponded to the measured activity patterns. (212)Pb was found to leave the tumor through the blood at a rate which decreased with tumor mass. Our results suggest that the proposed method, termed DART (diffusing alpha-emitters radiation therapy), may potentially be useful for the treatment of human patients.