Theranostic personalized nuclear medicine using Lutetium-177 (177Lu) as the therapeutic isotope has been shown to extend the median overall survival of patients suffering from neuroendocrine tumors (NETs) (Strosberg et al. 2021) and to extend the progression-free survival and overall survival of people treated for advanced metastatic castration-resistant prostate cancer (mCRPC) (Sartor et al. 2021), both of which are challenging to treat in people with refractory cancers.
Data from the National Program of Cancer Registries and National Cancer Institute Surveillance, Epidemiology and End Results Program suggest over 36,000 people are diagnosed each year in the United States (US) with NETs and prevalence data suggest many more are suffering in silence without a proper diagnosis and treatment options. Incidence of prostate cancer is increasing in the US, with a 2015 model by Scher et al. (2015) predicting approximately 39,000 annual mCRPC diagnoses in 2020, and the American Cancer Society estimating that approximately 34,000 deaths occurred in 2021 due to prostate cancer (American Cancer Society 2021). People with both types of diagnosis are in need of new therapeutic options to extend and maintain their quality of life.
While 177Lu based therapy has been expanding in North America, especially in larger research hospitals, there are still perceived barriers to adoption that can prevent smaller sites, such as outpatient and more rural, community-based clinics, from offering such programs. While smaller sites may offer diagnostic nuclear medicine services, there are different regulatory requirements and radiation safety challenges inherent to therapeutic nuclear medicine that may be addressed with the correct guidance and support.
The radiation safety challenges associated with a 177Lu therapy program are less than that of other therapeutic isotopes, such as 131I, due to its lower energy gamma emissions and lack of volatility. Despite this, the development of a radiation safety program to support the addition of a new therapeutic isotope requires a short-term time and resource investment, which can be challenging for medical Radiation Safety Officers (RSOs) as their roles constantly evolve (Berry et al. 2018). A panel of radiation safety experts from across Canada and the United States was assembled and tasked with documenting operational experience and best practice guidelines to act as a reference for RSOs tasked with or interested in expanding their radiation safety program to support a 177Lu therapy program.
The target audience for this set of guidelines is a radiation safety professional looking to start a 177Lu-based therapy program at their institution. The goal is that, with this guide as a reference, more radiation safety professionals will be able to support the implementation of 177Lu-based therapy at their institutions, thus improving the availability of these treatments and improving outcomes for cancer patients. Note that because the authors’ experience is limited to Canada and the United States, the recommendations of this document are presented from this regulatory perspective alone. The authors believe that the general themes of this paper are relevant in any country; however, local licensing and regulatory requirements must be reviewed and considered during the implementation of any program.
MATERIALS AND METHODS
A focus group consisting of 11 Radiation Safety Officers and Radiation Safety Technologists representing 10 different medical institutions across the United States and Canada was assembled. Experience levels varied, but each individual had been involved with the implementation or ongoing support of a 177Lu therapy program at the clinic or hospital they represented. Most panelists had experience with standard of care treatment using US Food and Drug Administration (US FDA) approved Lutathera (Advanced Accelerator Applications), with additional experience supporting a variety of other 177Lu products in various stages of clinical trials including Betalutin (Nordic Nanovector) and 177Lu-PSMA-617 (Advanced Accelerator Applications), now known as Pluvicto. Most sites represented by the panelists treated 1 to 4 177Lu patients per week, with one site seeing up to 20 patients per week.
It is important to note that the advice presented in this paper is based primarily on panelists’ experience to date with Lutathera treatment of a relatively limited number of patients. With the recent FDA approval of Pluvicto (lutetium Lu-177 vipivotide tetraxetan), panelists are expecting the number of patients treated at their sites to increase significantly. This will likely affect various aspects of the radiation safety experience, and some discussion of the anticipated changes is included in this paper.
A list of 36 questions was prepared by the panel coordinators covering a variety of topics on the practical implementation of a radiation safety program to support 177Lu therapy. A series of two discussion meetings was held with the panelists in June and September 2021 to discuss their responses to these questions and gather operational experience on radiation safety considerations in a 177Lu therapy program. Written responses were received from all participants and the general consensus was summarized in this paper. Panelists actively participated in the review of this summary to ensure their perspectives were accurately represented. Responses are grouped into the following three categories: facility layout and design; radiation safety program; and drug management and patient care.
FACILITY LAYOUT AND DESIGN
Due to its primarily beta emissions, with low energy and low intensity gamma, 177Lu as a therapeutic isotope offers significant economic and practical advantages over higher energy gamma emitters such as 131I. At all sites represented by the panelists, 177Lu therapy is performed on an outpatient basis with very limited exceptions in which in-patient therapy was performed on previously admitted patients. Most sites did not install fixed shielding in a treatment room specifically for the purposes of 177Lu therapy, although some made use of a shielded room previously designed for 131I therapy. At many sites represented by this panel, 177Lu therapy (Lutathera) is routinely performed in non-dedicated space, typically a standard nuclear medicine room and sometimes a general infusion or hematology room. Especially when using non-dedicated space, access to the patient room and assigned washroom are restricted after the patient has left until radiation safety support staff can survey, decontaminate (if required), and release the rooms for general use.
It is important to note that a site-specific shielding design assessment or dose estimate is typically required as part of the licensing process. The methodology proposed by Madsen et al. (2006) to evaluate shielding requirements for a positron emitting tomography facilities can be adapted for 177Lu by using the specific gamma constant and shielding factors for 177Lu. The dose calculated for this assessment depends on the activity injected, the number of patients treated and the duration of their stay. The introduction of more frequent Lu-177-PSMA-617 is expected to increase the workload and may require the use of shielding where it was previously not necessary. Mobile shields can also be a cost-effective option if additional shielding is required. With a half-value layer of about 0.5 mm lead (0.542 mm) (Smith and Stabin 2012) for 177Lu, even mobile diagnostic x-ray barriers can effectively cut dose rates in half. One site that regularly treated multiple patients at a time in one room used mobile shields to reduce overall exposure to staff entering the room.
When considering a room for use in 177Lu outpatient therapy, panelists recommend paying particular attention to the washroom, especially the toilet. Of the areas a patient interacts with during their treatment, the washroom is the most likely area to become contaminated. Many 177Lu-labelled therapeutic agents are excreted rapidly through urine, with approximately 50% of the injected activity excreted within 6 h for 177Lu Dotatate (Kwekkeboom et al. 2001) and 4 h for PSMA-617 (Kurth et al. 2018). One of the primary considerations when selecting a patient room for therapy should be the availability of an attached dedicated washroom. Eliminating the need for a patient to traverse a hallway to access the washroom reduces the likelihood of contamination spread to publicly accessible areas.
Multiple panelists experienced situations in which strong flush toilets caused the spread of contamination within the washroom. While the preference is to select a toilet with lower pressure or adjust the pressure downwards, limitations in some facilities led panelists to install a lid on the toilet or instruct patients to position an absorbent pad over the opening prior to flushing. Additionally, it is recommended that staff confirm the toilet flushes without clogging before starting each person’s therapy.
A critical consideration when preparing a site for 177Lu therapy is to ensure sufficient room for waste storage. Some suppliers or radiopharmacies may allow customers to return waste for disposal. Contact the supplier to determine if this is an option, as it will significantly decrease the amount of space required.
With a half-life of approximately 7 d (6.647 d) (Eckerman and Endo 2008), decay storage followed by disposal as non-radioactive medical waste is a cost-effective strategy, if permitted by local regulations. For a site accustomed to short-lived diagnostic isotopes only, 177Lu waste will require longer storage than the current layout may allow, and additional waste storage space may need to be identified. Waste typically consists of discarded personal protective equipment (PPE), absorbent pads, infusion supplies (including sharps) and contaminated paper used to cover surfaces. Contaminated waste generated from a single patient typically fits into a 1-gallon container.
The most common decay storage strategy adopted by the panelists is to store waste for 10 half-lives (approximately 70 d) before a final survey to ensure it is indistinguishable from background prior to disposal. Others perform a scheduled monthly survey of all 177Lu waste and release all undetectable bags. It is important to note that high activity material, such as an unused patient dose, will likely need to be decayed longer than 10 half-lives prior to disposal. Some suppliers or radiopharmacies may allow customers to return unused doses and/or waste materials for disposal. Contact the local supplier to determine if this is an option.
Lutetium-177 may be prepared using two different sources of stable isotopes (lutetium-176 or ytterbium-176) that require different waste management. When developing a waste strategy, it is essential to determine if the presence of the impurity 177mLu is expected in the product to be used.2 Lutetium-177 produced via direct neutron irradiation of 176Lu, also referred to as “carrier added” contains a metastable 177mLu impurity (Dash et al. 2015). With a half-life of approximately 160 d (160.4 d) (Eckerman and Endo 2008), 177mLu will not decay away in the same manner. In some cases, this can prevent the adoption of a decay storage strategy for waste management. For example, US Nuclear Regulatory Commission (US NRC) regulations require waste with a half-life greater than 120 d, including 177mLu containing wastes, to be disposed as low-level radioactive waste (US NRC 2004). Of the panelists who had experience with 177mLu, all noted that its presence significantly changes the waste strategy required, either requiring longer storage time (if decay storage is permitted) or requiring disposal through a waste broker.
RADIATION SAFETY PROGRAM
If not already authorized/licensed for 177Lu, an organization must typically apply to a local regulator to authorize its use. The application process and type of authorization/license required will vary depending on local regulations, but this will often require amendments to the radiation safety program. General guidance for development of a radiation safety program is presented in this section. Recommendations are based on American and Canadian experience, but the general concepts should be relevant globally. Radiopharmaceutical manufacturers often offer a regulatory package or licensing guide that can be a valuable resource for information specific to the local regulatory environment and application process. Contact the product vendor for this information.
Organizations applying for a nuclear medicine license in the US will generally need to identify an authorized user to supervise the use of radioactive materials at the site. This is a physician who has been certified in the relevant specialty by a medical board recognized by the US NRC or who meets a specific combination of training and work experience in this specialty. More details on the requirements for authorized users are provided by Baldwin et al. (2015).
In many radiation safety programs, the approval of an internal radiation safety committee is required before major changes can be made to the program or license. The timeframe required to add a new isotope to a license or commence a new treatment/clinical trial varied widely among panelists, with timeframes estimated from a few weeks to many months, but it was generally agreed that radiation safety review was not the most significant delay to starting a new therapy. Introduction of a new program is a multidisciplinary effort, and it will require input from a variety of other groups including ethics boards, financial reviews and procurement/materials management. Panelists noted that other factors, including physician availability, were more likely to delay the start of a program.
While the details of the radiation safety review process are unique to every site, the following topics were highlighted by the panel as common items for review: the amount of activity to be used per treatment and stored on site; exposure to staff; patient release instructions and dose estimates to caregivers; and waste management planning, which has been discussed in the previous section.
The activity possession limit on the license should be carefully considered at this stage. This limit applies to all activity a site has on hand, including activity to be injected, activity from cancelled patients and waste other than human excreta. The license must have sufficient room to accommodate the build-up of 177Lu in the facility, especially if treating multiple patients a week. Because 177Lu will not decay away as quickly as short-lived diagnostic isotopes, it is important to consider the build-up of activity over time. The residual activity in waste vials and infusion sets will contribute to this, but the possibility of sudden patient cancellations should also be considered. If the dose for a given patient is shipped, but the scheduled patient is not treated, this unused activity will count against the license possession limit. Note that some manufacturers will allow return of unused patient doses. Contact the manufacturer to investigate if this is an option.
Panelists’ experience indicated that annual doses to staff delivering 177Lu therapy were minimal relative to other nuclear medicine programs. This is supported in the literature, with annual individual external whole-body doses reported from 0.5 to 1.5 mSv to staff most involved in the care of patients being injected with 177Lu Dotatate (Calais and Turner 2014; Berry et al. 2020). Others have reported external dose accumulation to nursing staff ranging from 10 to 50 μSv per treatment day (Calais and Turner 2014; Nelson and Sheetz 2019). While dose rates outside a therapy room were reported to be minimal by panelists and in the literature by Nelson and Sheetz (2019), a conservative calculation of the potential exposure to workers and members of the public in surrounding areas is typically required as part of a radiation safety review.
The patient release criteria at each site was derived from the International Commission on Radiological Protection (ICRP) recommended dose constraint of 5 mSv per episode to relatives, visitors and caregivers (ICRP 2007) or the US NRC dose limit of 5 mSv to this same group. The specific limits set at each site varied among panelists. Most sites implemented a dose-rate-based limit, in which patients were only released when the dose rate measured at a given distance from their body was below a given limit. These limits varied from about 40 to 90 μSv h−1 at 1 m. Only one site noted an instance in which the dose rate from a patient exceeded the limit at the completion of therapy, a result of impaired renal function. Other sites adopted an activity-based criteria, in which a patient is simply released at the completion of therapy provided the activity injected was below a specified limit. These limits were justified with a conservative calculation of caregiver exposure following administration of a given activity and ensuring this dose was below 5 mSv. A detailed example of the justification for an activity-based release limit is provided by Olmstead et al. (2015).
Lutetium-177 contamination is readily detectable on a typical beta-sensitive contamination survey meter, such as a pancake style Geiger Mueller (GM) detector. An approximate 4-pi efficiency value of 20% is used by the McMaster University Health Physics department for direct surface contamination readings with a pancake-style GM detector. If an individual were to become contaminated with 177Lu during a spill or adverse event, there is the potential for significant skin dose. Should a skin contamination event occur, the dose to the basal layer of the skin can be calculated using a dose conversion factor of 1.2 mGy cm2 h−1 kBq−1. This dose conversion factor was determined using VARSKIN+ software (Hamby et al. 2021) for an area density of 7 mGy cm−2 and a contamination area of 1 cm2.
DRUG MANAGEMENT AND PATIENT CARE
Not all sites scheduled patients on a particular day, but for those that did, Tuesdays were a common choice. This allows time to prepare the room, conduct the therapy, and take down and release the room afterwards. Panelists recommended scheduling delivery of the activity for the day before treatment, allowing a buffer in the event of manufacturing or shipping delays. Providing a lockbox in a reception or shipping area allows greater tolerance of changes to shipping schedules, since doses can be received after hours when nuclear medicine or radiation safety staff may not be present on site. An alternate solution adopted by some institutions was the use of security staff to escort delivery personnel to a locked storage area for drop off after hours and on weekends.
Before injection, the treatment room and washroom should be prepared by papering surfaces to protect them from contamination. Panelists noted that only the surfaces most likely to become contaminated need to be covered. This includes areas such as the floor and wall immediately surrounding the toilet, the toilet seat, and the sink handles (Nelson and Sheetz 2019; Berry et al. 2020; Maughan et al. 2021). Paper or an absorbent pad should also be placed on the patient chair or bed in case of incontinence. An example room papering strategy provided by one of the panelists is pictured in Fig. 1. Other mitigation strategies suggested to prevent contamination spread due to patient incontinence were to allow patients to wear street clothes, which will contain any contaminated droplets, instead of open hospital gowns or providing paper shorts to wear with a gown.
Although the total time required for administration and monitoring of the patient after dosing varies depending on the product used or trial protocol, most patients will spend 4 to 8 hours on site during a Lutathera treatment. During this time a staff member, often a nurse or nuclear medicine technologist, is typically assigned to the patient. It is important that this staff member minimize their exposure by maintaining distance from the patient but be available to attend to the needs of the patient. If a dose-rate-based limit is used to release patients, a nuclear medicine technologist or radiation safety staff member will perform the final measurement on the patient prior to release. Initial feedback from panelists on their experience to date with PSMA-617 indicates that administration of PSMA-617 can be accomplished in as little as 1 hour.
One of the more common 177Lu therapies administered at panelist sites was Lutathera (Advanced Accelerator Applications, London, England). The prescribing information accompanying this product requires intravenous administration (IV), either using an infusion pump or by gravity in certain cases. Many of the sites used an infusion pump for administration, placing the dose vial inline between a saline bag and the pump. This setup is described in further detail by Maughan et al. (2021). This infusion pump setup is advantageous from a radiation safety perspective because the vial containing the activity can sit in the base of a shielded pig, effectively limiting radiation fields to a small cone above the vial. For sites administering via gravity infusion, IV bags were often shielded in plexiglass with a thickness greater than 0.5 cm to stop beta emissions. Syringe shields were used when administering other 177Lu products indicated for bolus injection.
Adverse events, while rare, can occur during therapy and it is important to have plans in place to manage these. One possibility is extravasation when using intravenous (IV) lines for administration. This can result in significant doses to the skin as the activity remains close to the injection site for an extended period. Patients should be monitored for signs of extravasation during infusion, and staff should be prepared to immediately respond using compression, elevation, and heat to attempt to distribute the activity away from the site. Discussion of extravasation cases and the recommended response are presented by Berry and Kendrick (2022) and Fisher and Liverett (2022). The US NRC is reviewing whether extravasations should be reported as a medical event. Plans should also be in place to allow a therapy patient to be admitted overnight in the event of an adverse reaction or other complication such as an electrolyte imbalance. Panelists recommend having an inpatient room available that can be prepared on short notice to accommodate a therapy patient with appropriate contamination control and radiation safety support.
Because the dose to others resulting from exposure to a patient treated with 177Lu has the potential to exceed 1 mSv (Olmstead et al. 2015; Nelson and Sheetz 2019), local regulations will typically require a licensee to provide patients with written instructions on actions to take to maintain these doses as low as reasonably achievable. All panelist sites provided such instructions to all 177Lu therapy patients, with some setting timelines for restrictions based on the methodology published by Underwood et al. (2021).
Panelists were divided on the use of wallet cards, with some choosing to issue these to all 177Lu patients upon release and others avoiding this practice. Panelists highly recommended issuing wallet cards if the site is in an area where patients are likely to encounter radiation detectors in public areas. These include radiation detectors deployed at public ferry terminals or tunnels leading into the city. These wallet cards typically include information on the patient’s therapy including the date, isotope, total activity administered, and radiation safety contact information. Examples of wallet cards used by the panelists are provided in Fig. 2.
Establishment of a safe, effective outpatient 177Lu therapy program in an institution with no prior experience in nuclear medicine therapy is feasible and can be done with less physical changes to a facility (shielding modifications) than other common therapeutic isotopes, such as 131I. Local regulations vary from place to place, and radiation safety staff must be aware of their regulatory requirements before pursuing this venture, but the collective operational experience and best practices presented here will help provide a starting point.
Overall, 177Lu therapy offered as part of a theranostics program is a promising tool in the fight to treat a variety of cancers, extending survival time for patients who only have access to current end of stage options. This novel therapy can offer much needed access to quality care in community settings. Adoption of 177Lu therapy in clinics and hospitals is picking up and will only continue to expand as new therapeutic agents receive approval for use in humans, in earlier lines of treatment, and across more cancer types, making the set-up of a 177Lu therapy program very enticing.
The authors of this paper were offered compensation for their time by POINT Biopharma. Some authors accepted; some authors did not.
American Cancer Society. Cancer facts & figures 2021. Atlanta, GA: American Cancer Society; 2021.
Baldwin JA, Bag AK, White SL, Palot-Manzil FF, O'Malley JP. All you need to know as an authorized user. AJR Am J Roentgenol 205:251–258; 2015. DOI:10.2214/AJR.14.13283.
Berry K, Kendrick J. Lutetium-177 radiopharmaceutical therapy extravasation lessons learned, Health Phys 123:160–164; 2022. DOI: 10.1097/HP.0000000000001558.
Berry K, Edwards B, Kendrick J. Three four years of experience treating patients with Lutathera. In: Proceedings of the 15th International Congress of the International Radiation Protection
Association. Seoul: The Korean Association for Radiation Protection
; 2020: T4.4-O0221.
Berry K, Elder D, Kroger L. The evolving role of the medical radiation safety officer. Health Phys 115: 628–636; 2018. DOI:10.1097/hp.0000000000000949.
Calais PJ, Turner JH. Radiation safety of outpatient 177
Lu-octreotate radiopeptide therapy of neuroendocrine tumors. Ann Nucl Med 28:531–539; 2014. DOI:10.1007/s12149-014-0843-8.
Dash A, Pillai MRA, Knapp FF. Production of 177
Lu for targeted radionuclide therapy: available options. Nucl Med Molec Imag 49:85–107; 2015. DOI:10.1007/s13139-014-0315-z.
Eckerman K, Endo A. Nuclear decay data for dosimetric calculations. ICRP Publication 107; Ann ICRP 38:7–96; 2008. DOI:10.1016/j.icrp.2008.10.004.
Fisher DR, Liverett M. Radiopharmaceutical extravasation: pragmatic radiation protection
. Health Phys 122:537–539; 2022. DOI:10.1097/hp.0000000000001538.
Hamby DM, Mangini CD, Luitjens JM, Boozer DL, Tucker ZG, Rose CT, Flora RS. Varskin+1.0 a computer code for skin contamination and dosimetry assessments. Corvallis, OR: US NRC; 2021.
ICRP. The 2007 recommendations of the International Commission on Radiological Protection. Oxford: ICRP; Publication 10; Ann ICRP37:1–332; 2007. DOI:10.1016/j.icrp.2007.10.003.
Kurth J, Krause BJ, Schwarzenböck SM, Stegger L, Schäfers M, Rahbar K. External radiation exposure, excretion, and effective half-life in (177)lu-psma-targeted therapies. EJNMMI Res 8:32; 2018. DOI:10.1186/s13550-018-0386-4.
Kwekkeboom DJ, Bakker WH, Kooij PP, Konijnenberg MW, Srinivasan A, Erion JL, Schmidt MA, Bugaj JL, de Jong M, Krenning EP. [177lu-dotaotyr3]octreotate: comparison with [111in-dtpao]octreotide in patients. Eur J Nucl Med 28:1319–1325; 2001. DOI:10.1007/s002590100574.
Madsen MT, Anderson JA, Halama JR, Kleck J, Simpkin DJ, Votaw JR, Wendt RE III, Williams LE, Yester MV. AAPM task group 108: PET and PET/CT shielding requirements. Med Phys 33:4–15; 2006. DOI:10.1118/1.2135911.
Maughan NM, Kim H, Hao Y, Unangst S, Roach MC Jr., Garcia-Ramirez JL, Amurao M, Luechtefeld D, Abdin K, Altman MB, Banks A, Riepe M, Bovard E, Jenkins S, Zoberi JE. Initial experience and lessons learned with implementing lutetium-177-dotatate radiopharmaceutical therapy in a radiation oncology-based program. Brachyther 20:237–247; 2021. DOI:10.1016/j.brachy.2020.07.004.
Nelson KL, Sheetz MA. Radiation safety observations associated with 177
Lu dotatate patients. Health Phys 117:680–687; 2019. DOI:10.1097/hp.0000000000001122.
Olmstead C, Cruz K, Stodilka R, Zabel P, Wolfson R. Quantifying public radiation exposure related to lutetium-177 octreotate therapy for the development of a safe outpatient treatment protocol. Nucl Med Commun 36:129–34; 2015. DOI:10.1097/mnm.0000000000000232.
Sartor O, de Bono J, Chi KN, Fizazi K, Herrmann K, Rahbar K, Tagawa ST, Nordquist LT, Vaishampayan N, El-Haddad G, Park CH, Beer TM, Armour A, Pérez-Contreras WJ, DeSilvio M, Kpamegan E, Gericke G, Messmann RA, Morris MJ, Krause BJ. Lutetium-177–psma-617 for metastatic castration-resistant prostate cancer. New England J Med 385:1091–1103; 2021. DOI:10.1056/NEJMoa2107322.
Scher HI, Solo K, Valant J, Todd MB, Mehra M. Prevalence of prostate cancer clinical states and mortality in the united states: estimates using a dynamic progression model. PLoS One 10:e0139440; 2015. DOI:10.1371/journal.pone.0139440.
Smith DS, Stabin MG. Exposure rate constants and lead shielding values for over 1,100 radionuclides. Health Phys 102:271–291; 2012. DOI:10.1097/hp.0b013e318235153a.
Strosberg JR, Caplin ME, Kunz PL, Ruszniewski PB, Bodei L, Hendifar A, Mittra E, Wolin EM, Yao JC, Pavel ME, Grande E, Van Cutsem E, Seregni E, Duarte H, Gericke G, Bartalotta A, Mariani MF, Demange A, Mutevelic S, Krenning EP. (177)Lu-dotatate plus long-acting octreotide versus high-dose long-acting octreotide in patients with midgut neuroendocrine tumours (netter-1): final overall survival and long-term safety results from an open-label, randomised, controlled, phase 3 trial. Lancet Oncol 22:1752–1763; 2021. DOI:10.1016/s1470-2045(21)00572-6.
Underwood J, Sturchio G, Arnold S. Patient release and instructions for lutetium dotatate radiopharmaceutical therapy. Health Phys 121:160–165; 2021. DOI:10.1097/hp.0000000000001425.
US Nuclear Regulatory Commission. NRC regulatory issue summary 2004-17: revised decay-in-storage provisions for the storage of radioactive waste containing byproduct material. Washington, DC: US NRC; 2004.