Beta-particle Sources Research Articles

CTNI-50. UPDATE REPORT OF THE RESPECT-GBM PHASE I/IIA DOSE ESCALATION TRIAL OF RHENIUM-186 NANOLIPOSOME (186RNL) IN RECURRENT GLIOMA [RGBM] VIA CONVECTION ENHANCED DELIVERY (CED)

Abstract BACKGROUND A Phase1/2a dose-escalation trial was initiated to determine the safety and recommended phase2 186RNL-dose(RP2D). Liposomal-rhenium-186(186RNL) is a source of high-energy beta-particles with gamma-photons representing attractive brain CED properties. METHODS A 3 + 3 Phase1 design was implemented per protocol [modified-Fibonacci dosing sequence]. We report safety and overall survival (OS) in 27 patients assigned to cohorts1-8. Patients with biopsy proven recurrent glioma had computerized treatment planning and placement of up to 5 intracranial catheter(s) single CED-186RNL administration. Whole body planar and SPECT/CT imaging through ~1 week following treatment was performed. Patients were followed for safety, sufficiency of delivery and OS. The significance of variation in OS was assessed with a 2-sided logrank test with α = 0.05. RESULTS Cohorts dosing ranged from 1mCi-in-0.6mL to 41.5mCi-in-16.3ml, MTD not reached, and no CED failures. No dose limiting toxicities were observed. Most common AEs were pre-existing GBM related signs/symptoms [weakness, fatigue, headache, seizure, scalp discomfort after CED] and >80% of AEs unrelated/unlikely relationship. Median absorbed radiation dose to the tumor (MARDT) was 308.4 Gy (8.9 Gy to 739.5 Gy). Patients were stratified by MARDT (< 100 Gy, ≥100 Gy). In all patients (N = 27), the median overall survival (OS) was 8 months (m), 95% CI 5 m to 13 m). In those receiving <100 Gy (N = 10), the median OS was 5 m (95% CI 1 m to 11 m) and in those with ≥ 100 Gy (N = 17) the median was 12 m (95% CI 5 m to 30 m), p < 0.001. CONCLUSION A single administration of 186RNL by CED in recurrent glioma patients is feasible, safe, and potentially effective in increasing overall survival when >100Gy radiation is delivered to the tumor. A RP2D of 22.3mCi in 8.8mL was selected for patients with tumor size of ≤20mL in the planned Phase 2B.

Persistent luminescence of ZrO2:Tb3+ after beta particle irradiation for dosimetry applications

In this work, we report the Persistent Luminescence (PLUM) of ZrO2:Tb3+ samples synthesized by a conventional solid-state reaction and its performance in radiation dosimetry. X-ray diffraction shows the formation of the monoclinic phase of ZrO2 and the doping of the samples with Tb3+ ions and a mixture of Tb2O3. The ZrO2:Tb3+ 1% sample was exposed to beta particle irradiation in a dose range from 0.5 to 256 Gy. Immediately after removing the beta particle source, the PLUM response was measured for 600 s. The integrated area of the PLUM decay curves shows a sublinear dependence in the dose range from 0.5 to 64 Gy. The TL glow curve of the ZrO2:Tb3+ 1% sample showed two maxima at 79 and 150 °C after beta particle irradiation, suggesting that the trapping states associated with the maximum at 79 °C are responsible for the PLUM at room temperature. Computational deconvolution showed that the maximum at 79 °C consisted of two traps with first-order kinetics. The results suggest that the ZrO2:Tb3+ 1% sample has potential applications as a dosimeter for beta particle irradiation.

RADT-20. REPORT OF THE RESPECT-GBM™ PHASE I/IIA DOSE ESCALATION TRIAL OF RHENIUM-186 NANOLIPOSOME (186RNL) IN RECURRENT GLIOMA VIA CONVECTION ENHANCED DELIVERY (CED) & PLANNED PHASE IIB TRIAL

Abstract A phase I/IIa dose escalation trial was initiated to determine the safety and recommended phase II dose (RP2D) of 186RNL in patients with recurrent glioma. Liposomal rhenium-186 (186RNL) is a source of high energy beta particles and gamma photons with attractive properties for brain CED.Patients with biopsy proven recurrent glioma had computerized treatment planning and placement of up to 4 intracranial catheter(s). Each patient received a single administration of 186RNL by CED. Whole body planar and SPECT/CT imaging from days 1-8 following treatment was performed. Patients were followed for safety, sufficiency of delivery and overall survival. Twenty-one patients across 6 dose escalation cohorts received 1.0-22.3mCi in a volume of 0.6-8.8mL. Mean tumor volume was 8.3mL, patients were heavily pretreated (mean 1.7 recurrences) with poor prognostic factors. There were no CED failures. Mean absorbed radiation dose to the tumor (MARDT) was 271Gy. No dose limiting toxicities were observed. Patients were stratified by MARDT. Those receiving > 100Gy MARDT (n=12) had a median and mean overall survival of 129.9 (95% CI 35.1 to 169.3) and 99.5 ± 19 weeks respectively with 3 patients alive. Patients receiving ≤ 100Gy MARDT (n=9) had a median and mean overall survival of 22.4 (95% CI 6.6 to 45.4) and 24.7 ± 4.8 weeks respectively, none are alive. Kaplan Meier analysis of overall survival for patients receiving MARDT greater than 100Gy vs. those with ≤ 100Gy showed a statistically significant difference in overall survival (p< 0.001).A single administration of 186RNL by CED in recurrent glioma patients is feasible, safe, and potentially effective in increasing overall survival when > 100Gy radiation is delivered to the tumor. A RP2D of 22.3mCi in 8.8mL was selected for patients with tumor size of ≤ 15mL in the planned phase 2b trial. The PIIb trial design and comparative survival data will also be presented.

277O The ReSPECT-GBM™ phase I/IIa trial of rhenium-186 nanoliposome (186RNL) in recurrent glioma via convection enhanced delivery (CED) and planned phase IIb trial

A phase I/IIa dose escalation trial was initiated to determine the safety and recommended phase II dose (RP2D) of 186RNL in patients with recurrent glioma. 186RNL is a source of high energy beta and gamma particles. We report the safety, feasibility, overall survival (OS), RP2D and proposed phase IIb clinical plan.

Betavoltaic cell based on Ni/β-Ga2O3 and 63Ni source

The parameters of betavoltaic cells based on a Ni/β-Ga2O3 Schottky barrier diode and beta-particle source containing 63Ni are evaluated. Monte Carlo simulation is used to calculate the depth-dependent generation rate of excess carriers produced by beta-radiation from 63Ni source. It is shown that the dependence can be described by the exponential function exp(−z/z0) with z0 equal to 1.3 μm. The short circuit current, open circuit voltage, and maximum power are calculated for the Schottky barrier with parameters obtained from the electron beam induced current studies of Ni Schottky barriers formed on n-type β-Ga2O3.

CTNI-29. SAFETY AND FEASIBILITY OF RHENIUM-186 NANOLIPOSOME (186RNL) IN RECURRENT GLIOMA: THE RESPECT™ PHASE 1 TRIAL

Abstract BACKGROUND Liposomal rhenium-186 (186RNL) is a potent source of beta particles with short path length, variable dose rate, high radiation density and gamma emission. Preclinically, 186RNL delivered via convection enhanced delivery (CED) achieves very high doses of targeted radiation with a wide therapeutic index. We report the results of ReSPECT, the first in man, dose escalation phase 1 trial of 186RNL in recurrent glioma. METHODS Following computer assisted treatment planning and placement of intracranial catheter(s), we performed a single administration of 186RNL by CED. We obtained whole body planar and SPECT/CT imaging on days 1-8 following treatment for dosimetry and distribution and followed patients for safety, progression and survival. RESULTS Twenty-one patients across 7 cohorts received 1.0-22.3mCi in a volume of 0.6-8.80mL. Mean tumor volume was 8.3mL (0.9-22.8mL). Patients had a mean of 1.7 recurrences, 5 received prior bevacizumab. Overall, 19/21 patients and all after cohort 4 had grade 4 glioma (glioblastoma). We used a CED rate of 5-20µl/min per catheter, with 1-4 catheters used per patient. Mean absorbed radiation dose to the tumor was 255Gy (8.9-740Gy) while exposure outside the brain was negligible. The mean percentage tumor in the treated volume (Tu/Tv) was 60.3% (19.8%-100%). Thus far, we have observed no dose limiting toxicities, one grade 3 treatment related adverse event (AEs), and the majority of AEs were mild in intensity. The incidence and severity of AEs did not correlate with increasing dose. Mean Tu/Tv in patients not receiving prior bevacizumab was 75% vs. 48% in those that had. Thus far, overall survival (OS) in 16 bevacizumab naïve patients is 49 weeks with 7 (44%) patients still alive and a positive correlation of OS to Tu/Tv. CONCLUSIONS 186RNL achieves high absorbed doses without significant toxicity with favorable overall survival.

Evaluation of an airborne alpha and beta particle detection capability using an environmental continuous air monitor system

We evaluate the ability of the Canberra Alpha Beta Environmental Continuous Air Monitor (ECAM) to detect and quantify airborne radiological contamination. The ECAM essentially consists of a passively-implanted planar silicon (PIPS) detector near a particulate filter through which outside air is pulled. Three years’ worth of background measurements on three different systems were assessed and calibrated to compensate for changing conditions and develop an average background response for the systems. The ECAM was also exposed to several radionuclides of interest, including 235U and 239Pu, to measure the response to alpha and beta particle sources. Both standard calibration sources and custom sources consisting of aqueous radioisotope solutions absorbed into clean filters. The ECAM responses to these sources were then scaled to quantities of interest and injected on the averaged background. Various alarm algorithms were evaluated on the source-injected spectra for minimum detectable air concentration for a given false alarm rate. Even in the worst case, the ECAM was able to detect radionuclides of interest at 10% of the Derived Response Level (DRL) for each isotope based on early-phase Protective Action Guides (PAG). Quantification of the radionuclides was also evaluated for the various algorithms, with mixed results, but overall clearly indicating the optimal algorithms for alpha and beta particle alarm and quantification. Finally, a limited evaluation of the beta particle detection efficiency points to a detection energy threshold of approximately 290 keV.

InGaP electron spectrometer for high temperature environments

In this work, a 200 μm diameter InGaP (GaInP) p+-i-n+ mesa photodiode was studied across the temperature range 100 °C to 20 °C for the development of a temperature-tolerant electron spectrometer. The depletion layer thickness of the InGaP device was 5 μm. The performance of the InGaP detector was analysed under dark conditions and then under the illumination of a 183 MBq 63Ni radioisotope beta particle source. The InGaP photodiode was connected to a custom-made low-noise charge-sensitive preamplifier to realise a particle counting electron spectrometer. Beta spectra were collected at temperatures up to 100 °C with the InGaP device reverse biased at 5 V. The spectrum accumulated at 20 °C was compared with the spectrum predicted using Monte Carlo simulations; good agreement was found between the predicted and experimental spectra. The work is of importance for the development of electron spectrometers that can be used for planetary and space science missions to environments of high temperature or extreme radiation (e.g. Mercury, Jupiter’s moon Europa, near-Sun comets), as well as terrestrial applications.

Biomolecular Analysis of Beta Dose-Dependent Cutaneous Radiation Injury in a Porcine Model.

While cutaneous radiation injury (CRI) is generally referenced as a consequence of a nuclear attack, it can also be caused by less dangerous events such as the use of dirty bombs, industrial radiological accidents, or accidental overexposure of beta (β) particle or gamma (γ) radiation sources in medical procedures. Although the gross clinical consequences of these injuries have been well documented, relatively little is known about the molecular changes underlying the progression of pathology. Here we describe a porcine model of cutaneous radiation injury after skin was exposed to strontium-90 b particle at doses of 16-42 Gy and characterize the anatomical and molecular changes over 70 days. The results show that irradiated sites displayed dosedependent increases in erythema and moist desquamation that peaked between days 35 and 42. Dose-dependent histopathological changes were observed, with higher doses exhibiting increased inflammation and epidermal hyperplasia beyond day 35. Furthermore, immunohistochemistry showed that exposure to 37 Gy β-particle radiation decreased epidermal cell proliferation and desmosomal junction proteins at day 70, suggesting compromised epidermal integrity. Metabolomic analysis of biopsies revealed dose- and time-dependent changes as high as 252-fold in several metabolites not previously linked to CRI. These alterations were seen in pathways reflecting protein degradation, oxidative stress, eicosanoid production, collagen matrix remodeling, mitochondrial stress, cell membrane composition and vascular disruption. Taken together, these data show that exposure to high doses of β particle damaged the molecular processes underlying skin integrity to a greater extent and for a longer period of time than has been shown previously. These findings further understanding of radiation-induced skin injury and serve as a foundation for the development and testing of potential therapeutics to treat CRI.

Gafchromic XRQA-2 film for Strontium-90/Yttrium-90 (Sr-90/Y-90) Detection

Gafchromic XRQA-2 radiochromic film is an effective tool for quality assurance and dose assessment in kilovoltage radiotherapy and diagnostic applications. This work is done to study the response of Gafchromic XRQA-2 film for beta particle detection. Materials investigated are the beta particle source, Sr-90/Y-90 and Gafchromic XRQA-2 film. The film is exposed to Sr-90/Y-90 for different duration of time and scanned with flatbed scanner. The film is analyzed by using a ImageJ software in the red mode. The result shows that the net reflected optical density (Net ROD) increased linearly with increase in time. The Net ROD and time integrated specific surface activity increased linearly with time. The Net ROD for Sr-90/Y-90 is from 0.00 to 0.13. Thus, the Net ROD is highly related to the duration of time exposed to the beta source.

Comparative study of kinetic parameters induced by different excitation sources: using a novel and user-friendly glow curve deconvolution spreadsheet

In this work, we performed a comparison study between the kinetic parameters associated to the KCl:Eu2+ crystal, which is excited separately with ultraviolet light and a source of beta particles. To obtain the kinetic parameters easily (peak and trap parameters), the glow curve deconvolution technique was implemented in a novel and friendly spreadsheet, the KCl:Eu2+ crystal was used as an example. Also, was employed a new mathematical equation to realize the glow curve deconvolution (based on Kiti’s original expressions) and was designed a low cost electronic configuration was implemented. In literature it is reported that, regardless of the excitation source, the glow curves of KCl:Eu2+ crystal have a similar shape. However, when the overlapped peaks are analyzed in detail (using their kinetic parameters), only some peaks of both glow curves have the same kinetic parameters. Some peaks appear only when beta particles are used, while other peaks appear only when UV light is used. The similarity between the glow curves, produced with ionizing and non-ionizing radiation, could indicate a common damage mechanism behind both irradiation processes.

Investigation of a temperature tolerant InGaP (GaInP) converter layer for a 63Ni betavoltaic cell

A prototype InGaP p+–i–n+ mesa photodiode was studied for its potential as the energy conversion device in a 63Ni betavoltaic cell; its electrical performance was analysed across the temperature range −20 °C to 100 °C. The results show that the InGaP detector when illuminated with a laboratory 63Ni radioisotope beta particle source had a maximum output power of 0.92 pW at −20 °C, this value decreased at higher temperatures. A decrease in the open circuit voltage and in the cell internal conversion efficiency were also observed when the temperature was increased: at −20 °C, the open circuit voltage and the cell internal conversion efficiency had values of 0.69 V and 4%, respectively. A short circuit current of 4.5 pA was measured at −20 °C.

Experimental and Simulation Analysis of Radiation of the Beta Emitting Sources in a Magnetic Field.

Objective:The behavior of beta particles under the magnetic field was investigated both theoretically and experimentally based on the assumption of reducing the damage to the normal tissues created by using magnetic field in radionuclide therapy.Methods:A water-filled spherical medium and a beta particle source was formed by using Geant4 simulation software for the theoretical study. After applying a homogenous magnetic field, the volume of points at which the particles interact with the medium was calculated by determining particle range. The range of beta particles was examined using yttrium-90 source and Gafchromic films for the experimental study. The setup was kept in normal room conditions and in the magnetic resonance imaging device. Then the irradiated films were analyzed by creating isodose curves.Results:With the increase of the magnetic field, the number of hits at the center was increased, but the number of hits at the outer boundaries decreased inversely proportional to the strength of the magnetic field. The change perpendicular to the magnetic field was greater as compared to the change parallel to the magnetic field. The volume of hits of beta particles got smaller with the increase of the magnetic field.Conclusion:When magnetic field is increased, the decrease in the number of interactions at the outer boundaries became more pronounced in the perpendicular direction to the magnetic field. The effect of magnetic field was more apparent for higher energy beta particles than lower energy particles.

Spectral response evaluation of plastic rod scintillators asposition sensitive beta particle detectors

In this work, a simple position sensitive detector based on rod plastic scintillators was developed for detection of beta particles. The detection setup consisted of a plastic-based rod detector (BC400) coupled to a PMT at one side. A Promethium-147 having about 7 mCi activity was used as a beta particle source. It was shown that the spectral response of this detector can provide useful information about the incident position of the beta particles.

Physical Parameters of Phosphor Layers and their Effects on the Device Properties of Beta‐radioluminescent Nuclear Batteries

AbstractA series of phosphor layers (ZnS:Cu‐Large, ZnS:Cu‐Small, and Y2O2S:Eu) precipitated with varying mass thicknesses were prepared using a homogeneous precipitation method. Radioluminescence (RL), the light emitted from phosphor materials immediately upon beta particle radiation, was measured at room temperature using RL spectra under 4.89 mCi cm−2 63 Ni and 2.23 mCi cm−2 147 Pm beta particle sources, respectively. The RL properties, such as emission intensity, are affected by the mass thickness of the phosphor layers. In this work, the performance of beta‐radioluminescent nuclear batteries with the aforementioned phosphor layers as intermediate absorbers was analyzed and discussed. The current–voltage characteristics of the nuclear batteries revealed the effect of the physical parameters of the phosphor layers. The maximum output power of the batteries increased approximately linearly with increasing RL intensity for the three types of phosphors under excitation by different beta sources.

High-Accuracy Miniature Dew Point Sensor and Instrument

This paper introduces a novel dew point sensor that is characterized by miniature size and accuracy that matches the well-known and much larger chilled mirror sensors. The new sensor is based on the beta voltaic principle, a relatively new principle of physics. It consists mainly of a radioactive beta-particle source and a silicon p-n junction. If no water condensation exists on the surface of the p-n junction, the beta particles enter the junction and generate a steady dc voltage. Once a condensed layer of water forms, the beta particles are blocked and the voltage produced by the p-n junction falls. The sensor will be very useful in new instruments and industrial applications that demand a miniature and highly accurate dew point sensor.

Characteristics of a new polymer gel for high-dose gradient dosimetry using a micro optical CT scanner

The properties of a new polymer gel with two sensitivities, made specifically for high-dose-gradient dosimetry, were investigated. The measurements were performed at NIST using a 1 cm×1 cm calibrated 60Co field, and a 1 cm active diameter 90Sr/ 90Y beta particle source. A high-resolution laser CT scanner was used to quantify the response. The results show that the high-sensitivity gel responds linearly to the absorbed dose for doses from 0.5 up to 15 Gy, while the low-sensitivity one is linear up to 225 Gy. For both radiation types, the gel response remains stable in time up to a month after the irradiation. The response of the gel was found to have no dose rate dependence for dose rates ranging from 3.7 to 15 mGy/s. Within the measurement uncertainty, the gel response is more sensitive for beta particles than high energy photons.

Betavoltaics using scandium tritide and contact potential difference

Tritium-powered betavoltaic micropower sources using contact potential difference (CPD) are demonstrated. Thermally stable scandium tritide thin films with a surface activity of 15mCi∕cm2 were used as the beta particle source. The electrical field created by the work function difference between the ScT film and a platinum or copper electrode was used to separate the beta-generated electrical charge carriers. Open circuit voltages of 0.5 and 0.16V and short circuit current densities of 2.7 and 5.3nA∕cm2 were achieved for gaseous and solid dielectric media-based CPD cells, respectively.

Characteristics of a 85Kr beta-particle source applied in Series 1 reference irradiations of TMDIS-1 direct ion storage dosemeters

Characteristics necessary to specify an ISO 6980 Series 1 reference radiation field were determined for a commercially available 85Kr beta-particle source, using a BEAM EGS4 Monte Carlo code. The characteristics include residual maximum beta energy, E(res), and the uniformity of the dose rate over the calibration area. The E(res) and the uniformity were also determined experimentally, using an extrapolation ionization chamber (EC) and a 0.2 cm3 parallel plate ionization chamber, respectively. The depth-dose curve measured with the EC gave a value 0.62 MeV for the E(res). Series 2 90Sr + 90Y and Series 1(85) Kr beta-particle sources calibrated for H(p)(0.07) at the secondary standard dosimetry laboratory (SSDL) of STUK were used to determine the energy and angular responses of DIS-1 direct ion storage dosemeters. The averaged zero angle H(p)(0.07) responses to the 90Sr + 90Y and 85Kr reference radiations were 135 and 80%, respectively. The responses were normalized to 100%, H(p)(0.07) response to 137Cs photon radiation.

Nuclear Batteries Using Tritium and Thin Film Hydrogenated Amorphous Silicon

p-i-n junction nuclear devices have been made using tritiated amorphous silicon in the intrinsic region. In this unique device, tritium passivates defects and at the same time is an internal source of beta particles. The beta particles traverse the i-layer and through impact ionization, electron-hole pairs are generated. These charges are separated by the built-in field of the p-i-n junction and electrical power is generated. The power from the devices is about 0.2 nW cm-2 in a device of 400 nm thickness. The decay of tritium leads to the formation of dangling bonds and strain related defects in the silicon lattice. These defects lead to a decrease in the effective width of the space charge region and thereby to an increase in the recombination rate of carriers. As a consequence the electric power decreases with time. To overcome this degradation in performance, delta layered devices were made by selectively introducing tritium into the intrinsic region by modulating the tritium gas fraction during film deposition. The electric power from devices with a delta layer have better stability.