WAM-A - Special Session: Chelation Orlando IV 08:10 - 11:45
|
| Chair(s): Luiz Bertelli, Raymond Guilmette
|
| |
WAM-A.0
08:10 Introduction and Announcements
|
WAM-A.1
08:15 Dosimetry of a Wound Contaminated with 238Pu During and After Medical Intervention JA Klumpp*, Los Alamos National Laboratory
; L Bertelli, Los Alamos National Laboratory; D Poudel, Los Alamos National Laboratory; S Dumit, Los Alamos National Laboratory
Abstract: This presentation considers internal dosimetry aspects of a wound contaminated with 238Pu at Los Alamos National Laboratory. The incident initially appeared to be a simple external contamination, and radiation protection personnel were only alerted that an intake had happened by an elevated bioassay sample. Since there seemed to be no plausible mechanism of intake, the elevated sample was assumed to have been contaminated in the counting laboratory. However, a wound count using a NaI counter was ordered as a precaution, and discovered that a significant quantity of plutonium had been deposited beneath the skin, in spite of the fact that there was no visible wound. The contamination was excised and the employee was given a course of DTPA.. We will discuss how the dose was estimated during treatment, and compare various prospective and retrospective methods for evaluating the dose. In particular, we will discuss how the dose estimate evolved during and following treatment. We will also discuss the considerations regarding how and when to collect bioassay data while the individual was under chelation.
|
WAM-A.2
08:45 Early Wound Assessment: The Derived Reference Level (DRL) SL Sugarman*, Summit Exercises and Training
Abstract: The roll of the health physicist is an important one when it comes to emergency response, be it providing recommendations to field personnel or assisting healthcare personnel. While providing internal dose information is often thought as requiring the collection of indicated samples and performing complicated modeling/calculations, this level of detail is not always required during the early stages. The initial stages of response and/or decision making require that a few basic questions be answered: Is it a problem, yes or no? If the answer is yes, is it a big problem or a small problem? How do I need to proceed while keeping the magnitude of the problem in proportion to the suggested response? The key word in the initial stages is “magnitude.” The Derived Reference Level (DRL) is a tool that was developed by the Radiation Emergency Assistance Center/Training Site (REAC/TS) and is based on data contained in Dose Coefficients for Intakes of Radionuclides Via Contaminated Wounds (Toohey, Bertelli, Sugarman, Wiley, Christensen: V2, 2014). It is intended to be an activity level against which information obtained early in the response can be compared to help assess the magnitude of a potential intake of radioactive material via a contaminated wound. How was this tool developed? How is it used? What are the gaps, and how are they being addressed? While the DRL is not intended to provide a definitive dose estimate – this should be done via more traditional bioassay methods such as urinalysis, etc. – it is a tool that can be used to help inform decisions when waiting on sample collection and analysis may be detrimental to achieving maximum efficacy with medical countermeasures.
|
WAM-A.3
09:00 Chelation Therapy at the Savannah River Site 1986-2006: A Personal Recollection TL LaBone*, MJW Companies
Abstract: I was an operational internal dosimetrist from 1986 to 2006 at the US Department of Energy facility currently called the Savannah River Site (SRS). With respect to chelation therapy, this was an interesting time and place to work because
• Large quantities of plutonium were handled at SRS during this time period in support of the nuclear weapons program and for the space program (radioisotope thermoelectric generators).
• The nature of the work made relatively small occupational intakes of plutonium by workers unavoidable.
• The SRS medical staff considered DTPA to be a safe and effective drug, and did not hesitate to use it when not medically contradicted and with the consent of the patient.
• Over the years we had to evaluate numerous small intakes of plutonium by individuals that were treated with one or two doses of DTPA.
• Stakeholders had a desire (and expectation) to have firm estimates of internal dose within weeks of an event.
• Chelation perturbs the biokinetics of plutonium excretion, rendering evaluation performed with standard biokinetic models and methods equivocal.
Given all this, there was a strong need for models and methods that could be used to evaluate urinary excretion of plutonium, with acceptable predictive power, before the effects of chelation had subsided. I have not been active in this arena for over 15 years, so I have little to tell you that might be considered state-of-the-art. Rather, I will offer my recollections of the events that drove the development of chelation models during this time period and lessons learned. My hope is that this will be of some value to current practitioners and model developers.
|
WAM-A.4
09:30 Health Physics and Medical Management of a Pu-238 Contaminated Wound WM Findley*, MJW Corporation, formerly Savannah River Site
Abstract: On 14, June 2010, a waste repackaging operator at the Savannah River Site sustained a puncture wound to the right index finger during a “flagging” operation resulting in an initial estimated deposition of 4.4 kBq of predominantly 238Pu transuranic alpha activity. Medical management included multiple surgical excisions in the first nine days post-intake with 71 DTPA intravenous chelation therapy administrations over a 315-day period post-intake. Excretion was monitored via timed urine samples and fecal samples with retention monitored via in-vivo measurements of the wound site, lymph nodes, liver, and skeleton. The protracted chelation regimen and requisite medical monitoring will be detailed. The use of a rapid urinalysis screening method and the advantages it provided with regard to guiding DTPA therapy will be discussed. The intake was evaluated using the NCRP 156 wound models with an assigned committed effective dose (CED) of 0.316 Sv. Long term monitoring data and beneficial outcomes will be provided in conclusion.
|
WAM-A.5
10:30 Chelation Modeling: The Use of Ad Hoc Models and Approaches to Overcome a Dose Assessment Challenge S Dumit*, Los Alamos National Laboratory
; L Bertelli, Los Alamos National Laboratory; JA Klumpp, Los Alamos National Laboratory; D Poudel, Los Alamos National Laboratory; T Waters, Los Alamos National Laboratory
Abstract: Chelating agents are administered to treat intakes from radioactive elements such as plutonium, americium, and curium. These drugs may be used as a medical countermeasure after nuclear accidents and terrorist acts. Chelating agents are known to increase the rate of elimination of actinides from the body. The enhancement of the actinide’s excretion alters its normal biokinetics, posing a dose assessment challenge. Thus, the standard biokinetic models cannot be directly applied to the chelation-affected bioassay data in order to assess the radiation dose. The present study reviews the scientific literature, from the early 1970s until the present, on the different studies that focused on developing new chelation models and/or modeling of bioassay data affected by chelation treatment. Although scientific progress has been achieved, there is currently no consensus chelation model available, even after almost fifty years of research. This presentation acknowledges the efforts made by different research groups, highlighting the different methodology used in some of these studies. Finally, this study puts into perspective where we were, where we are, and where we are heading to in regards to chelation modeling.
|
WAM-A.6
10:45 CANCELLED - Efficacy of DTPA Chelation of Actinides – The REAC/TS Experience RE Toohey*, M. Chew Associates
; RE Goans, MJW Corporation; J Davis, ORAU-REAC/TS; CJ Iddins, ORAU-REAC/TS
Abstract: Cancelled
|
WAM-A.7
11:00 DTPA efficacy after wound contamination with Am: comparison of various administration protocols A Van der Meeren*, CEA
; S Lamart, CEA; NM Griffiths, CEA
Abstract: An established experimental wound model was used to evaluate DTPA efficacy following Americium (Am) contamination. Am nitrate or Am contained in MOX (Pu, U Mixed Oxide) was introduced into deep wounds made in the hind limb of rats. Various DTPA administration regimens were used and the effects were compared on urinary excretion, local retention, and systemic deposition. At 1 or 7 days post-contamination, no differences were observed between DTPA intravenous or local administration at 30 minutes or 2 hours on urinary excretion or systemic tissue retention. Repeated intravenous treatment led to greater increased urinary excretion compared with a single dose. This suggests that some locally-retained Am is still accessible to DTPA over time. A first step for determination of DTPA treatment efficacy is analysis of experimental data using a statistical tool developed in the laboratory. Differential consequences on committed effective dose will be the next milestone.
|
WAM-A.8
11:15 New decorporation strategies for reducing risk from intakes of lanthanides and actinides RJ Abergel*, University of California, Berkeley and Lawrence Berkeley National Laboratory
; JA Rees, Lawrence Berkeley National Laboratory; DD An, Lawrence Berkeley National Laboratory
Abstract: The threat of a major radiological event presents a danger of not only large-scale external radiation exposure of the population but also internal contamination with radionuclides, including actinides and lanthanide fission products. Numerous factors influence the potential health effects after contamination, including the contaminant physicochemical properties or the contamination route, but preventing or reversing tissue deposition remain the most efficacious ways to reduce the risk associated with intake. Current treatment options are limited and address only a few of the many radioisotopes that would pose a significant medical threat after a nuclear event.
To seek regulatory approval for new decorporation agents or new formulations, a number of efficacy and safety studies must respond to the selective criteria of the Animal Rule from the U.S. Food and Drug Administration (FDA). The FDA approved the first clinical study for a new f-element decorporation agent 3,4,3-LI(1,2-HOPO) in August 2014. The Investigational New Drug (IND) application was the result of a large number of studies performed to optimize the drug candidate, demonstrate its safety, activity and efficacy, and establish a mechanism of action. These studies will be summarized, with an accent on the extensive regulatory process guiding such development work. Finally, while initially targeted radionuclides included isotopes from the actinide series (Am, Cf, Cm, Pu, U), recent developments in the medical use of f-elements (Gd, Lu, Ac, Th) have uncovered a persisting need for such decorporation agents much beyond the national security threat. A perspective on applying 3,4,3-LI(1,2-HOPO) to prevent internal Gd deposition and subsequent toxicity from MRI contrast agents will be given.
Part of this work was supported by the Medical Countermeasures Against Radiological Threats Consortium of the National Institute of Allergy and Infectious Diseases (#HHSN272201000046C) and the Biomedical Advanced Research and Development Authority (#IPIAA12OS99609), through the U.S. Department of Energy under Contract #DE-AC02-05CH11231.
|
WAM-A.9
11:30 Recent Research On Improved Chelating Agents For Decorporation Radionuclides RA Guilmette*, Ray Guilmette & Associates
; Guilmette
Abstract: Reduction of body content of internally deposited radionuclides using decorporating agents has been done for over 60 years, primarily on exposed workers in various nuclear industries. During this period, most events with exposed workers consisted of one or a few cases, which in general could be readily handled by occupational medicine groups trained in administering this type of treatment. Subsequent to the terrorist events that occurred on 11SEP01, the U. S. Government recognized the need to address the possibilities of other types of terrorist events that might involve the use of chemical, biological, radiological or nuclear materials (CBRN). Thus, an extensive research program was initiated in the mid-2000s that dealt with the discovery and development of medical countermeasures for all of the aforementioned threats. Part of this program, administered by the National Institute of Allergy and Infectious Diseases (NIAID), focused on improving decorporation therapy for a relatively large number of members of the public exposed to radionuclides considered to be most likely used in radiological dispersal events. This paper will elaborate on the research progress accomplished in the last decade in developing, testing and licensing new chelating agents or new formulations of previously existing chelators for decorporation. Most of this research has focused on improving the removal of actinides such as Pu and Am from the body, in particular the development of orally efficacious formulations of DTPA. Other radionuclides have also been targeted, e.g., isotopes of Cs and Sr, and these results will be shown as well. The current status of the various programs will also be described as well as outlooks for the future.
|
