Diethylenetriaminepentaacetic acid (DTPA) is an attractive decorporation agent that can enhance the excretion of radioactive actinides such as plutonium, americium, and curium after a radiological incident. However, DTPA is excreted in a short period of time after administration. Several formulations have been developed to improve DTPA pharmacokinetics properties. In this project, liposomes were prepared facilely from soy lecithin as a nanocarrier for pulmonary delivery of Zn–DTPA. Lipid hydration, reverse phase evaporation, and mechanical sonication were three methods evaluated for the preparation of liposome-encapsulated Zn-DTPA (lipo-Zn-DTPA). Mechanical sonication was the method of choice due to simple apparatus and facile preparation. Lipo-Zn–DTPA exhibited a hydrodynamic diameter of 178 ± 2 nm and a spherical shape. The loading capacity and encapsulation efficiency of Zn–DTPA were 41 ± 5 mg/g and 10% ± 1%, respectively. Lyophilization of lipo-Zn–DTPA for extended storage did not affect the amount of encapsulated drug or damage the structure of liposomes. An in vivo cytotoxicity test confirmed no serious adverse effect of Zn–DTPA encapsulated lecithin liposomes in rats.

Diethylenetriaminepentaacetate (DTPA) is an approved chemical agent for decorporation of internalized actinides.During a radiological or nuclear incident, inhalation of radioactive material into the lungs is one of the main paths of hazardous exposure.High affinity of DTPA toward actinides makes it a suitable actinide decorporation agent that accelerates their excretion from the human body.Polymeric nanoparticles are ideal for use in prolonging drug release, as they are biocompatible, non-toxic, and have been approved for therapeutic use by the Federal Drug Administration.Poly lactic-co-glycolic acid (PLGA) was chosen for this research as previous literature has shown that PLGA NPs would delay the drug release of other therapeutic agents.PLGA NPs encapsulating Zn-DTPA were synthesized for the first time to extend the DTPA release in human lungs.Since the physicochemical properties of a particle such as its size and functional groups can influence its uptake by lung cells and tissues in vivo, the synthesized PLGA NPs encapsulating Zn-DTPA were characterized by transmission electron microscopy, Fourier-transform infrared spectroscopy, and dynamic light scattering.The loading capacity of Zn-DTPA in the PLGA NPs achieved in this formulation was determined to be 10(±1)% (w/w) through use of Liquid Chromatography-Mass Spectrometry (LC-MS).Extended release of Zn-DTPA from the PLGA NPs into simulated lung fluid was confirmed via dialysis experiments using continuous Ultraviolet (UV) absorbance monitoring.LC-MS was also used to demonstrate the extended release of DTPA from these PLGA NPs; a significantly longer half-time was achieved compared to that obtained for Zn-DTPA itself.As the dialysis lung fluid volume increased, longer half-times were observed for both Zn-DT-PA and Zn-DTPA encapsulated by PLGA NPs.Furthermore, as expected, decreasing the concentration of Zn-DTPA in dialysis experiments increased the half-time.The purpose of this study was to extend the drug release through an optimized formulation of DTPA encapsulated PLGA NPs as compared to the free DTPA treatment in vitro study.

3,4,3-LI(1,2-HOPO) has been identified as an excellent alternative for DTPA for decorporating actinides, such as Pu and Am, after internal contamination. Efforts have been focused on its application through oral administration. When 3,4,3-LI (1,2-HOPO) was encapsulated with biocompatible, biodegradable nanoparticles made of chitosan, its release from the nanoparticles to lung fluid, observed in in vitro experiments, exhibited an extended release profile. These observations were very encouraging, as this nanomedicine could lead to a reduction in the dosing frequency required to achieve the decorporation efficacy of unformulated 3,4,3-LI(1,2-HOPO) itself. In vivo release tests as well as actinide decorporation experiments, using an inhalation exposure animal model, will follow.

The Global Health Security Initiative (GHSI) established a laboratory network within the GHSI community to develop collective surge capacity for radionuclide bioassay in response to a radiological or nuclear emergency as a means of enhancing response capability, health outcomes and community resilience. GHSI partners conducted an exercise in collaboration with the WHO Radiation Emergency Medical Preparedness and Assistance Network and the IAEA Response and Assistance Network, to test the participating laboratories (18) for their capabilities in in vitro assay of biological samples, using a urine sample spiked with multiple high-risk radionuclides (90Sr, 106Ru, 137Cs, and 239Pu). Laboratories were required to submit their reports within 72 h following receipt of the sample, using a pre-formatted template, on the procedures, methods and techniques used to identify and quantify the radionuclides in the sample, as well as the bioassay results with a 95% confidence interval. All of the participating laboratories identified and measured all or some of the radionuclides in the sample. However, gaps were identified in both the procedures used to assay multiple radionuclides in one sample, as well as in the methods or techniques used to assay specific radionuclides in urine. Two-third of the participating laboratories had difficulties in determining all the radionuclides in the sample. Results from this exercise indicate that challenges remain with respect to ensuring that results are delivered in a timely, consistent and reliable manner to support medical interventions. Laboratories within the networks are encouraged to work together to develop and maintain collective capabilities and capacity for emergency bioassay, which is an important component of radiation emergency response.

This study was designed to assess the feasibility of a noninvasive urine specimen for the detection of proteins as indicators of internal exposure to ionizing radiation. Three groups of rats (five in each group) were intravenously injected with 1601 ± 376, 10,846 ± 591 and 48,467 ± 2812 Bq of (210)Po in citrate form. A sham-exposed control group of five rats was intravenously injected with sterile physiological saline. Daily urine samples were collected over 4 days following injection. Purification and pre-concentration of urinary proteins were carried out by ultrafiltration using a 3000 Da molecular weight cutoff membrane filter. The concentration of common urinary proteins, namely albumin, alpha-1-acid glycoprotein, immunoglobulins IgA and IgG, was measured by an enzyme-linked immunosorbent assay. Urinary excretion of albumin decreased dose-dependently (p < 0.05) 96 h post-injection relative to the control group. In contrast, no statistically significant effects were observed for other proteins tested. The dose-dependent decrease in urinary excretion of albumin observed in this study underscores the need for further research, which may lead to the discovery of new biomarkers that would reflect the changes in the primary target organs for deposition of (210)Po.

The Global Health Security Initiative (GHSI) established a laboratory network within the GHSI community to develop their collective surge capacity for radionuclide bioassay in response to a radiological or nuclear emergency. A recent exercise was conducted to test the participating laboratories for their capabilities in screening and in vitro assay of biological samples, performing internal dose assessment and providing advice on medical intervention, if necessary, using a urine sample spiked with a single radionuclide, 241Am. The laboratories were required to submit their reports according to the exercise schedule and using pre-formatted templates. Generally, the participating laboratories were found to be capable with respect to rapidly screening samples for radionuclide contamination, measuring the radionuclide in the samples, assessing the intake and radiation dose, and providing advice on medical intervention. However, gaps in bioassay measurement and dose assessment have been identified. The network may take steps to ensure that procedures and practices within this network be harmonised and a follow-up exercise be organised on a larger scale, with potential participation of laboratories from the networks coordinated by the International Atomic Energy Agency and the World Health Organization.

Nine laboratories participated in an intercomparison exercise organised by the European Radiation Dosimetry Group (EURADOS) for emergency radiobioassay involving four high-risk radionuclides (239Pu, 241Am, 90Sr and 226Ra). Diverse methods of analysis were used by the participating laboratories for the in vitro determination of each of the four radionuclides in urine samples. Almost all the methods used are sensitive enough to meet the requirements for emergency radiobioassay derived for this project in reference to the Clinical Decision Guide introduced by the NCRP. Results from most of the methods meet the requirements of ISO 28218 on accuracy in terms of relative bias and relative precision. However, some technical gaps have been identified. For example, some laboratories do not have the ability to assay samples containing 226Ra, and sample turnaround time would be expected to be much shorter than that reported by many laboratories, as timely results for internal contamination and early decisions on medical intervention are highly desired. Participating laboratories are expected to learn from each other on the methods used to improve the interoperability among these laboratories.

Nasal swabs and facial swipes have been used to screen potential internal radioactive contamination for decades. However, the ratio between the lung intake and the activity on a swab or a swipe varies according to the nature of the contaminant involved and the exposure conditions such as particle sizes of the contaminant and the humidity in the air. This paper reports the experimental results using stable La2O3 as an analog for actinide oxides, focusing on the most important parameters such as humidity, plume velocity, and facial condition at a fixed room temperature of 23 ± 2 °C. The results showed that the effects of humidity, plume velocity, and facial condition vary more on orofacial swipe/lung deposition ratios compared to nasal swab/lung deposition ratios. The amounts on nasal swabs tended to show smaller change with respect to parameters such as plume velocity, humidity, and skin moisture. The amounts on orofacial swipes varied by a factor of 10–15 among the samples collected across all parameters. Such variability would be expected to be even greater in a real-world scenario with a larger range of physiological and environmental conditions.

An international workshop on emergency radiobioassay was held in Ottawa, Canada, 1-3 September 2010. Sixty-five scientists and public health officials from five countries attended the workshop and gave 36 presentations. During the workshop, many considerations were raised, gaps identified, and recommendations given for emergency radiobioassay for both preparedness and response in case of a radiological or nuclear incident. In short, some bioassay methods and protocols need to be developed, validated, and exercised; national and international radiobioassay laboratory networks should be established; and communications and collaborations among public health officials, monitoring experts, and medical staff are encouraged. All these activities are required to make us better prepared for an RN emergency.

Population monitoring is an important component of radiological and nuclear emergency preparedness and response. Since 2002, Canada has been investing in developing national capabilities in radiological population monitoring. This paper summarizes Canada's efforts in developing methods and techniques in biological dosimetry and in vivo and in vitro bioassay techniques. There are still many gaps to fill that require further efforts. Integration of different monitoring methods and techniques in order to have the best assessment of radiation dose to support medical management and integration of Canada's efforts with international efforts are recommended.

The performance of the ORTEC(®) Detective™ as a field deployable tool for emergency urine bioassay of (137)Cs, (60)Co, (192)Ir, (169)Yb and (75)Se was evaluated against ANSI N13.30. The tested activity levels represent 10 % RL (reference level) and 1 % RL defined by [Li C., Vlahovich S., Dai X., Richardson R. B., Daka J. N. and Kramer G. H. Requirements for radiation emergency urine bioassay techniques for the public and first responders. Health Phys (in press, 99(5), 702-707 (2010)]. The tests were conducted for both single radionuclide and mixed radionuclides at two geometries, one conventional geometry (CG) and one improved geometry (IG) which improved the MDAs (minimum detectable amounts) by a factor of 1.6-2.7. The most challenging radionuclide was (169)Yb. The measurement of the mixture radionuclides for (169)Yb at the CG did not satisfy the ANSI N13.30 requirements even at 10 % RL. At 1 % RL, (169)Yb and (192)Ir were not detectable at either geometry, while the measurement of (60)Co in the mixed radionuclides satisfied the ANSI N13.30 requirements only at the IG.

241Am is one of the high-risk radionuclides that might be used in a terrorist attack. 241Am in urine bioassay can identify the contaminated individuals who need immediate medical intervention and decontamination. This paper compares three methods for the measurement of 241Am in urine, namely liquid scintillation counting (LSC), inductively coupled plasma mass spectrometry (ICP-MS) and gamma spectrometry (GS), at two levels, 20 and 2 Bq l(-1). All three methods satisfied the ANSI N13.30 radio-bioassay criteria for accuracy and repeatability. ICP-MS offered the best sensitivity and fastest sample turnaround; however, the ICP-MS system used in this work may not be available in many bioassay laboratories. LSC and GS are more commonly available instruments. GS requires minimal or no sample preparation, which makes it a good candidate method. Moreover, the sample throughput can be significantly improved if the GS and LSC methods are automated.

U-236 is present at ultra-trace levels in typical environmental and biological samples. Typically, it has been measured by highly sensitive techniques, such as accelerator mass spectrometry. This paper reports the measurement of U-236 in 20 human tissue samples using a sector field ICP-MS following automated SPE separation. The tissue samples were selected from one USTUR case, representing tissues/organs that are important for internal radiation assessment. Another uranium isotope, U-235, was also measured in the samples. The results for U-235 were compared with those obtained by alpha spectrometry. For most cases, results from the two methods were comparable, indicating that the measurement of U-236 in the samples is reliable.

An emergency urine bioassay method has been developed for the determination of (241)Am in human urine samples. The method is based on extraction chromatographic separation of (241)Am from urine on a single DGA (N,N,N',N'-tetraoctyldiglycolamide) resin column followed by liquid scintillation counting of (241)Am. The minimum detectable activity (MDA) for the method was 0.02 Bq. Considering the volume of urine sample (17.2 ml) used by the method; the MDA was 1.3 Bq l(-1). Measurement accuracy (relative bias, B(r)) and repeatability (relative precision, S(B)) of the method were found to be -3.4 and 8.9 %, respectively, when urine samples were spiked with (241)Am (20 Bq l(-1)). Excellent linearity (r(2) > 0.999) was established over the range of 2-200 Bq l(-1). The method was also found to be robust (S(B)=10.2 %) against matrix effects from different urine samples. Performance of the rapid bioassay method for accuracy and repeatability were evaluated against the performance criteria for radiobioassay (ANSI N13.30) and found to be in compliance. Considering the simplicity, excellent analytical figures of merit and fast sample turnaround time (<1 h), it is a very promising rapid bioassay method for supporting the medical response to an emergency where internal contamination of (241)Am is involved.