Samuel Glover

Significant systemic therapeutic effects of high-LET immunoradiation by 212Pb-trastuzumab against prostatic tumors of androgen-independent human prostate cancer in mice

The purpose of this study was to determine therapeutic effects and systemic toxicity of 212Pb-trastuzumab in an orthotopic model of human prostate cancer cells in nude mice. TCMC-Trastuzumab was radiolabeled with 212Pb. The 212Pb-trastuzumab generated from the procedure was intact and had high binding affinity with a dissociation constant (of 3.9±0.99 nM. PC-3MM2 cells, which expressed a lower level of HER2 both in culture and in tumors, were used in therapy studies. A single intravenous injection of 212Pb-trastuzumab reduced tumor growth by 60-80%, reduced aortic lymph node metastasis, and prolonged the survival of tumor-bearing mice. Treatment with 212Pb-trastuzumab did not cause significant changes in body weight, serum glutamic pyruvic transaminase (SGPT), blood urea nitrogen (BUN), hematological profiles, and histological morphology of several major organs of tumor-bearing mice. These findings suggest that a systemic delivery of 212Pb-trastuzumab could be an effective modality for management of advanced human prostate cancer.

School bus pollution and changes in the air quality at schools: a case study

Millions of children attending US schools are exposed to traffic-related air pollutants, including health-relevant ultrafine aerosols generated from school buses powered with diesel fuel. This case study was established in a midwestern (USA) metropolitan area to determine the concentration and elemental composition of aerosol in the vicinity of a public school during morning hours when the bus traffic in and out of the adjacent depot was especially intense. Simultaneous measurements were performed at a control site. The ambient aerosol was first characterized in real time using a particle size selective aerosol spectrometer and then continuously monitored at each site with a real-time non-size-selective instrument that detected particles of 20 nm to >1 microm. In addition, air samples were collected with PM2.5 Harvard Impactors and analyzed for elemental composition using the X-ray fluorescence technique (for 38 elements) and thermal-optical transmittance (for carbon). The measurements were conducted during two seasons: in March at ambient temperature around 0 degrees C and in May when it ranged mostly between 10 and 20 degrees C. The particle number concentration at the test site exhibited high temporal variability while it was time independent at the control site. Overall, the aerosol particle count at the school was 4.7 +/- 1.0 times (March) and 2.2 +/- 0.4 times (May) greater than at the control site. On some days, a 15 min-averaged particle number concentration showed significant correlation with the number of school bus arrivals and departures during these time intervals. On other days, the correlation was less than statistically significant. The 3 h time-averaged particle concentrations determined in the test site on days when the school buses operated were found to be more than two-fold greater (on average) than those measured on bus-free days at the same location, and this difference was statistically significant. Overall, the data suggest a possible association between the number of detected aerosol particles and the school bus traffic intensity. Analysis of the filter samples collected at the school site between 6:00 and 9:00 AM revealed higher concentrations of elemental carbon as compared to the control site (2.8 +/- 0.9 times in March and 3.1 +/- 1.1 times in May). The data collected in this case study suggest that school buses significantly contribute to exposure of children to aerosol pollutants (including diesel exhaust particles) in the school vicinity.

USTUR whole body case 0262: 33-y follow-up of Puo2 in a skin wound and associated axillary node

This whole body donation case (USTUR Registrant) involved two suspected PuO2 inhalation intakes, each indicated by a measurable Pu alpha activity in a single urine sample, followed about 1(1/2) y later by a puncture wound to the thumb while working in a Pu glovebox. The study is concerned with modelling simultaneously the biokinetics of deposition and retention in the respiratory tract and at the wound site; and the biokinetics of Pu subsequently transferred to other body organs, until the donors death. Urine samples taken after the wound incident had readily measurable Pu alpha activity over the next 14 y, before dropping below the minimum detectable excretion rate (<0.4 mBq d(-1)). The Registrant died about 33 y after the wound intake, at the age of 71, from hepatocellular carcinoma with extensive metastases. At autopsy, all major soft tissue organs were harvested for analysis of their 238Pu, 239+240Pu and 241Am content. The amount of 239+240Pu retained at the wound site was 68 +/- 7 Bq (1 SD), measured by low-energy planar Ge spectrometry. A further 56.0 +/- 1.2 Bq was retained in an associated axillary lymph node, measured by radiochemistry. Simultaneous mathematical analysis (modelling) of all in vivo urinary excretion data, together with the measured lung, thoracic lymph node, wound, axillary lymph node and systemic tissue contents at death, yielded estimated intake amounts of 757 and 1504 Bq, respectively, for the first and second inhalation incidents, and 204 Bq for the total wound intake. The inhaled Pu material was highly insoluble, with an estimated long-term absorption rate from the lungs of 2 x 10(-5) d(-1). The Pu material deposited at the wound site was mixed: approximately 14% was rapidly absorbed, approximately 49% was absorbed at the rate of about 6 x 10(-5) d(-1), and the remainder ( approximately 37%) was absorbed extremely slowly (at the rate of about 5 x 10(-6) d(-1)). Thus, it was estimated that only approximately 40% of the Pu initially deposited in the wound had been absorbed systemically over the 33-y period until the donors death. The biokinetic modelling also indicated that, in this individual case, some of the parameter values (rate constants) incorporated in the ICRP Publication 67 Pu model were up to a factor of 2 different from ICRPs recommended values (for reference man).

Measurement of the attenuation coefficient for Livermore Thoracic Phantom lungs fabricated using contemporary materials.

The University of Cincinnati has reproduced the original formulation for the Livermore Thoracic Phantom lungs using contemporary materials and has adopted the linear attenuation coefficient as the primary quality assurance parameter for evaluating the performance capabilities of these new lung phantoms. The Livermore Thoracic Phantom was originally fabricated in 1978 to intercalibrate detector systems used to measure plutonium and other low-energy, photon emitting radionuclides deposited in the respiratory tract. The linear attenuation coefficient is a critical performance indicator for these phantom lungs since the presence of any material with a high effective atomic number (where Z > or = 20) will make a significant change in the photoelectric cross section, the predominant mode of interaction for plutonium x rays. A set of test lungs was fabricated with KCl to introduce a known quantity of 40K in the phantom and to determine, by measurement and calculations, what change would be made to the attenuation coefficient at photon energies below 100 keV as a result of the modified formulation. The KCl increased the linear attenuation coefficient below 60 keV by more than a factor of two, which would produce a substantial systematic error in any subsequent calibration measurements performed with these modified phantom lungs. These results support use of the attenuation coefficient as an important performance indicator for the Livermore Thoracic Phantom lungs and also suggest that KCl not be added to the lung tissue substitute formulation as a means to incorporate 40K in the phantom for low energy calibrations.

In vivo measurement of 241Am in the lungs confounded by activity deposited in other organs.

AbstractRadioactive material deposited in multiple organs of the body is likely to confound a result of an in vivo measurement performed over the lungs, the most frequently monitored organ for occupational exposure. The significance of this interference was evaluated by measuring anthropometric torso phantoms containing lungs, liver, skeleton, and axillary lymph nodes, each with a precisely known quantity of 241Am uniformly distributed in the organs. Arrays of multiple high-resolution germanium detectors were positioned over organs within the torso phantom containing 241Am or over proximal organs without activity to determine the degree of measurement confounding due to photons emitted from other source organs. A set of four mathematical response functions describes the measured count rate with detectors positioned over each of the relevant organs and 241Am contained in the measured organ or one of the other organs selected as a confounder. Simultaneous solution of these equations by matrix algebra, where the diagonal terms of the matrix are calibration factors for a direct measurement of activity in an organ and the off-diagonal terms reflect the contribution (i.e., interference or cross-talk) produced by 241Am in a confounding organ, yields the activity deposited in each of the relevant organs. The matrix solution described in this paper represents a method for adjusting a result of 241Am measured directly in one organ for interferences that may arise from 241Am deposited elsewhere and represents a technically valid procedure to aid in evaluating internal dose based upon in vivo measurements for those radioactive materials known to deposit in multiple organs.

Morphology of actinide-rich particles released from the BOMARC accident and collected from soil post remediation

The physical, chemical, and radiological characteristics of material released to the environment from accidents involving nuclear weapon components are dependent upon many factors, especially the manner in which the material is released and delivered to the environment. These characteristics will also be influenced by physical and chemical effects associated with weathering if the material remains exposed to the environment for a long period of time. This study evaluates the morphological characteristics of particles released to the environment as a result of the 1960 BOMARC incident and compares these characteristics to those described following similar incidents at Thule, Greenland (1968) and Palomares, Spain (1966). Each of these incidents involved unique circumstances and conditions that distributed actinide-rich particles to the environment with a range of distinctive morphological characteristics. Morphological and surface elemental analyses were conducted on a set of discrete particles isolated from samples of post-remediated soil collected at McGuire Air Force Base, the site of the BOMARC incident. Scanning electron microscopy and complimentary energy dispersive X-ray spectroscopy were used to perform the analyses. Non-destructive analysis of uranium and plutonium contained in each particle was measured using high-resolution gamma spectrometry. Unique characteristics of the BOMARC samples include some particles exhibiting a smooth, crystalline texture and varying elemental surface distribution of uranium and plutonium, dependent on the particle’s morphology.

A calibration phantom for direct, in vivo measurement of 241Am in the axillary lymph nodes.

A calibration phantom was developed at the University of Cincinnati (UC) to determine detection efficiency and estimate the quantity of activity deposited in the axillary lymph nodes of a worker who had unknowingly sustained a wound contaminated with 241Am at some distant time in the past. This paper describes how the Livermore Torso Phantom was modified for calibrating direct, in vivo measurements of 241Am deposited in the axillary lymph nodes. Modifications involved milling a pair of parallel, flat bottom, cylindrical holes into the left and right shoulders (below the humeral head) of the Livermore Torso Phantom in which solid, 1.40-cm-diameter cylindrical rods were inserted. Each rod was fabricated using a muscle tissue substitute. One end of each rod contained a precisely known quantity of 241Am sealed in a 1-cm-diameter, 2.54-cm-deep well to simulate the axillary lymph nodes when inserted into the modified Livermore Torso Phantom. The fixed locations for the axillary lymph nodes in the phantom were determined according to the position of the Level I and the combined Level II + III axillary lymph nodes reported in the literature. Discrete calibration measurements for 241Am in the simulated axillary lymph nodes located in the right and left sides of the thorax were performed using pairs of high-resolution germanium detectors at UC and Lawrence Livermore National Laboratory. The percent efficiency for measuring the 59.5 keV photon from 241Am deposited in the right and left axillary lymph nodes using a pair of 3,000 mm2 detectors is 2.60 ± 0.03 counts &ggr;−1 and 5.45 ± 0.07 counts &ggr;−1, respectively. Activity deposited in the right and left axillary lymph nodes was found to contribute 12.5% and 19.7%, respectively, to a lung measurement and 1.2% and 0.2%, respectively, to a liver measurement. Thus, radioactive material mobilized from a wound in a finger or hand and deposited in the axillary lymph nodes has been shown to confound results of a direct, in vivo measurement of the lungs.

Compton background suppression with a multi-element scintillation detector using high speed data acquisition and digital signal processing

A multi-element scintillation detector, consisting of eight NaI(Tl)/BGO scintillators surrounding a single NaI(Tl)/CsI(Tl) scintillator, was initially developed for locating and measuring concealed special nuclear materials that emit primarily low energy photons. Signal digitizers and LabView virtual instrument (VI) subroutines process and analyze pulses from each of the dual scintillators to suppress Compton interactions occurring in the central detector and discriminate between low and high energy photon events occurring within NaI(Tl) and CsI(Tl) crystals, respectively. Digital signal processing significantly improved the signal-to-noise ratio of the central detector and greatly reduced the analog electronic equipment required in the same time.

Measurements of plutonium, 237Np, and 137Cs in the BCR 482 lichen reference material

Abstract Select anthropogenic radionuclides were measured in lichen reference material, BCR 482. This material was originally collected in Axalp, Switzerland in 1991 and is composed of the epiphytic lichen Pseudevernia furfuracea. Samples from three separate bottles of BCR 482 were analyzed for uranium, neptunium, and plutonium isotopes by inductively coupled plasma mass spectrometry and analyzed for 137Cs by gamma-ray spectrometry. The isotopic composition of the radionuclides measured in BCR 482 suggests contributions from both global fallout resulting from historical nuclear weapons testing and more volatile materials released following the Chernobyl accident.

Detection efficiency for measuring 241Am in axillary lymph nodes using different types and sizes of detectors.

Abstract The detection efficiency and interference susceptibility of four different types of low energy photon detectors, each with a unique geometric arrangement, were compared for direct measurement of 241Am deposited in the axillary lymph nodes. Although the most efficient detector was a single large 23,226 mm2 square phoswich detector, it was also the most susceptible to confounding depositions from activity deposited in adjacent organs. The array of two 2,800 mm2 high purity germanium detectors exhibited the highest efficiency per unit detector area with some resistance to confounding from activity deposited in the lungs. The array of two 4,560 mm2 NaI(Tl) detectors was the least susceptible to confounding and nearly as efficient per square millimeter as the high purity germanium detector array. Thus, selection of a detector system for in vivo measurement of activity deposited in the axillary lymph nodes should consider whether there is a likelihood for activity deposited in other organs, such as the lungs, skeleton, or liver, to create an interference that will confound the measurement result.