Original article
Quantifying public radiation exposure related to lutetium-177 octreotate therapy for the development of a safe outpatient treatment protocol Craig Olmsteada, Kyle Cruza, Robert Stodilkaa,b,c, Pamela Zabela,b,c and Robert Wolfsona Objectives Radionuclide therapies, including treatment of neuroendocrine tumors with lutetium-177 (Lu-177) octreotate, often involve hospital admission to minimize radiation exposure to the public. Overnight admission due to Lu-177 octreotate therapy incurs additional cost for the hospital and is an inconvenience for the patient. This study endeavors to characterize the potential radiation risk to caregivers and the public should Lu-177 octreotate therapies be performed on an outpatient basis.
Conclusion Given the low dose rate and cumulative levels of radiation measured, the results support that an outpatient Lu-177 octreotate treatment protocol would not jeopardize public safety. Nevertheless, the concept of ALARA still requires that detailed radiation safety protocols be developed for Lu-177 octreotate outpatients to minimize radiation exposure to family members, caregivers, and the general public. Nucl Med Commun 36:129–134 © 2015 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Materials and methods Dose rate measurements of radiation emanating from 10 patients were taken 30 min, 4, and 20 h after initiation of Lu-177 octreotate therapy. Instadose radiation dose measurement monitors were also placed around the patients’ rooms to assess the potential cumulative radiation exposure during the initial 30 min–4 h after treatment (simulating the hospital-based component of the outpatient model) as well as 4–20 h after treatment (simulating the discharged outpatient portion).
Nuclear Medicine Communications 2015, 36:129–134 Keywords: dosimetry, lutetium-177 octreotate, neuroendocrine tumors, peptide receptor radionuclide therapy, radiation a Department of Nuclear Medicine, London Health Sciences Centre, Victoria Campus, bDepartment of Medical Imaging, Western University and cLawson Health Research Institute, London, Ontario, Canada
Correspondence to Craig Olmstead, BMath, BSc, 298 Wortley Road, London, ON, Canada N6C 3R5 Tel: + 1 519 933 9101; fax: + 1 519 685 8500; e-mail: [email protected]
Results The mean recorded dose rate at 30 min, 4, and 20 h after therapy was 20.4, 14.0, and 6.6 μSv/h, respectively. The majority of the cumulative dose readings were below the minimum recordable threshold of 0.03 mSv, with a maximum dose recorded of 0.18 mSv.
Received 8 August 2014 Revised 22 September 2014 Accepted 23 September 2014
Introduction
surface, particularly SSTR-2, making them an ideal target for delivery of Lu-177 octreotate radiotherapy [2].
The conventional approach to oncologic management typically involves surgery, chemotherapy, and/or external-beam radiation therapy. Recent innovation in the field of molecular target-based therapy has advanced cancer care by tailoring patient treatment to the tumor’s unique cellular blueprints. Peptide receptor radionuclide therapy is one such class of modern molecular therapeutics; by targeting tumors that overexpress a specific receptor, a systemic therapy can be delivered in a more concentrated manner to the tumor with lower exposure to the native cells, thereby maximizing therapeutic delivery while minimizing toxicity to healthy tissue. The peptide receptor radionuclide therapy agent lutetium177 (Lu-177) octreotate is a radiolabelled somatostatin analog that binds preferentially to somatostatin transmembrane receptor (SSTR)-2, as well as to SSTR-3 and SSTR-5, although with weaker affinity [1]. Neuroendocrine tumors classically overexpress somatostatin receptors on their cell 0143-3636 © 2015 Wolters Kluwer Health | Lippincott Williams & Wilkins
Lu-177 octreotate treatment demonstrated therapeutic effectiveness by achieving complete remission, partial remission, or a minor response in 46% of patients [2]. The treatment is generally well tolerated, with patients most commonly exhibiting minor side effects such as hair thinning, nausea, vomiting, and abdominal discomfort [2]. Organ toxicity is uncommon; less than 10% of patients experience subacute hematological toxicity during the course of treatment, and overall rates of renal toxicity are similarly low [2,3]. In a standard course of consolidation treatment at London Health Sciences Centre, patients receive three to four doses of Lu-177 octreotate, administering between 5.7 and 7.4 GBq of activity, with successive therapies performed 2–3 months apart [4]. By way of its γ emissions, Lu-177 radiation exposure is a concern for those who may be in close proximity to the patient, particularly on the DOI: 10.1097/MNM.0000000000000232
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130 Nuclear Medicine Communications 2015, Vol 36 No 2
first day of treatment [5]. As a result of the substantial quantity of Lu-177 octreotate involved with the treatment, current practices in Canada require patients to be isolated in a lead-lined room for their first night after each dose administration to protect others from unnecessary radiation exposure. The required isolation is expensive and, for most patients, not medically warranted. Lu-177 octreotate therapy carries a considerable per-patient cost before including those associated with hospital admission; hence, money-saving measures are important to ensure its cost-effectiveness and therefore its continued availability for patients. The economic imperative to minimize costs is ever-present, and the current economic climate of tightened healthcare budgets only serves to reinforce this necessity. Furthermore, the inpatient model is overly restrictive on the large subset of highly functioning, otherwise healthy, patients who have to endure potentially unnecessary physical and emotional seclusion outside of their home. In addition, an overnight hospital stay increases the patient’s risk for nosocomial infections [6,7]. One study estimated the increased risk of developing a hospital-acquired infection from an additional day in hospital at 1.37% [7]. For these reasons, we have chosen to explore the possibility of eliminating the requirement for full-day isolation by demonstrating that the radiation exposure to others can be safely and effectively managed outside of the hospital setting. Currently, most treatment centers providing Lu-177 octreotate therapy do so only on an inpatient basis, with regulatory differences related to radiation exposure to the public being the primary constraint on how soon a patient undergoing therapy may be discharged from the hospital [5]. For example, in Germany, where more strict radiation regulations exist, patients who receive Lu-177 therapy may be admitted for periods lasting longer than one night, as opposed to those receiving treatment in Australia where less stringent radiation safety requirements allow for an outpatient protocol [5]. Additional work by Calais and Turner [8] in Australia has further supported the acceptability of Lu-177 octreotate therapy on an outpatient basis within that jurisdiction. In addition, dose rate measurements from patients in the Calais and Turner [8] study suggest that outpatient therapy may be feasible within Canada’s regulatory framework. Yet, even in many jurisdictions with lighter regulations, treatment centers often err on the side of caution, resulting in overnight hospital admissions in the absence of rigorous radiation exposure data. Lu-177 octreotate has favorable physical and biological properties in terms of minimizing radiation exposure to the public. The radioisotope undergoes beta decay to emit a low-to-medium-energy β particle, which is predominantly absorbed within the body of the patient, as well as γ-ray emissions of low abundance and low-to-
medium energy, thus minimizing the irradiation of nearby bystanders [5]. The biological excretion for Lu-177 is primarily through the urine and feces, which, for most patients, are easily contained and properly disposed [9]. By comparison, iodine-131, which is used in the treatment of differentiated thyroid carcinoma, has a considerably higher abundance of γ emissions and higher energy gamma rays relative to Lu-177, as seen in Table 1, resulting in a substantially higher specific γ coefficient [10–12]. It also has more routes of biologic excretion, including saliva and sweat [5,13,14]. Radioactive iodine therapies are performed on an outpatient basis at many treatment centers in Canada [15,] and we postulate that the radiation exposure to the public from Lu-177 octreotate outpatient therapy would be less than iodine-131. This article outlines the efforts undertaken at the London Health Sciences Centre’s Victoria campus to quantify the potential levels of public radiation exposure from Lu-177 octreotate therapy for the purpose of establishing the safety of an outpatient protocol.
Materials and methods This study analyzed the radiation emanating from Lu177 octreotate in patients treated at the London Health Sciences Centre. Inclusion criteria for study participation included all of the following: (a) an upcoming Lu-177 octreotate therapy at our institution; (b) an age of at least 18 years with capacity to consent to the research study; (c) ability to comply with the 20 h isolation rules within their designated hospital room; and (d) ability to comply with not tampering with the radiation detector devices utilized in the study. A total of 10 patients were approached to participate in the study, with all potential research subjects agreeing to be involved. The dose administered to these patients ranged between 7400 and 7550 MBq. Ethics approval for this study was granted by The University of Western Ontario Research Ethics Board for Health Sciences Research Involving Human Subjects. Radiation exposure was measured in two ways. First, dose rate measurements using a precalibrated Victoreen 450B-DE-SI (Victoreen, Cleveland, Ohio, USA), recorded in μSv/h were taken at 30 min, 4, and 20 h after infusion of Lu-177 octreotate. These time points were chosen because of their significance in converting the Table 1
Physical characteristics of iodine-131 and lutetium-177
Isotope
Half-life (days)
Iodine-131
8.02
Lutetium-177
6.65
γ emissions (energy) (keV)
γ emissions (abundance) (%)
284 364 642 113 208
6.1 81.2 7.3 6.2 10.4
Specific γ constant (μSv·m2/MBq·h) 0.063
0.0066
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Lu-177 octreotate radiation exposure Olmstead et al. 131
current inpatient protocol to an outpatient one. At 30 min, the patient voids for the first time after the Lu177 octreotate is administered and eliminates a significant quantity of radioactivity through the urine [9]. Because of the high amount of initial excretion, the postvoid reading was considered the more reliable and useful starting point of radiation measurement, especially when extrapolating through the remainder of the therapy. In addition, the patient is isolated during those initial 30 min, eliminating the possibility of exposure to others. The second and third measurement times, at 4 and 20 h, respectively, represent the intended time of discharge with an outpatient protocol and the current discharge time with an inpatient protocol. Each dose rate measurement was taken at a distance of 1 m away from the patient, at the level of the patient’s liver. In addition, direct ion technology dose measurements were obtained within and around the patient’s room to simulate cumulative radiation exposure to family members, caregivers, and the general public. These readings, in mSv, were collected over two time periods: at commencement of therapy until the 4 h mark and from the 4 h mark until the 20 h mark. To obtain these cumulative dose measurements, devices were set up in strategic locations throughout the patient’s room while undergoing treatment. There were eight locations: outside the room’s door, on the wall behind the toilet, above the patient’s bed (mounted to the ceiling), beneath the patient’s bed, and one on each wall within the room. Figures 1 and 2 provide a representative plan of the patient’s room with the location of each detector, and Table 2 details the distance from the center of the patient’s bed to each detector. The direct ion technology devices used for cumulative radiation measurements were Instadose pocket dosimeters (Mirion Technologies, San Ramon, California, USA). These dosimeters can register cumulative radiation doses as low as 0.03 mSv. The Instadose dosimeters were tested for linearity and constancy with a Lu-177 point source before being used in this study. Constancy, evaluated using the 16 devices employed in the study placed 1 m away from a 3.26 GBq source (at the time of initiation) for 2 h, resulted in a mean recorded dose of 0.11 mSv and a SD of 0.012 mSv. To determine the radiation-related safety of Lu-177 octreotate, measurements were analyzed against both absolute and relative standards of safety. For this study, our threshold for safety was 5 mSv/year for the patient’s primary caregiver [16], which is similar to current iodine131 outpatient therapies. Data on 10 iodine-131 therapies were drawn at random from deidentified radiation safety records at the London Health Sciences Centre, which are acquired as part of routine radiation decommissioning practice when performing iodine-131 outpatient therapies (1870–5785 MBq).
Fig. 1
D1 Toilet
Door to washroom D2 Chair
Bed M
D3
D5
D4 D8 Door to hallway Floor diagram of the patient’s room. D1, washroom; D2, west wall; D3, south wall; D4, east wall; D5, north wall; D8, outside door. M indicates the middle of the patient’s bed.
Fig. 2
Ceiling D6
M Bed D7 Floor Cross-section of the patient’s room. D6, ceiling; D7, lower bed frame. M indicates the middle of the patient’s bed.
Results As shown in Table 3, the measured dose rate values generally decreased over time as the activity of intravenously
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132 Nuclear Medicine Communications 2015, Vol 36 No 2
Table 2
Distance between the center of the patient’s bed and cumulative dose detectors
Distance from center of patient’s bed (m)
Table 3
Washroom (D1)
West wall (D2)
South wall (D3)
East wall (D4)
North wall (D5)
Ceiling (D6)
Lower bed frame (D7)
Outside door (D8)
3.83
1.24
1.98
1.88
1.17
1.47
0.56
2.54
Survey meter dose rate readings
Patient number 1 2 3 4 5 6 7 8 9 10 Largest observed value
30 min (postvoid)
4 h mark
Discharge
18.1 18.6 24 24 16.5 18.6 19 22 21 22 24
9.2 9.5 14.2 20 8.8 6.8 33a 10.7 15.5 12.7 33
3.1 1.8 7.2 20 7.5 4.4 11 3.6 4.3 3 20
Values are in μSv/h. Potentially erroneous reading; see the text for full discussion.
a
infused Lu-177 octreotate was progressively eliminated from the body. There were two exceptions to this general trend of decline. First, the dose rate from patient 4 did not drop after the 4 h mark but remained constant at 20 μSv/h at the 20 h mark; the finding can be explained by the high degree of somatostatin-avid tumor burden within this patient, resulting in high trapping rates and minimal biological excretion. Second, the dose rate from patient 7 increased at the 4 h mark when compared with the 30 min mark, but declined substantially by the 20 h mark. The 4 h dose rate reading for patient 7 is suspected to be erroneous; it was discovered after-the-fact that a similar but improperly calibrated monitor may have been used for that lone reading. However, as we have been unable to ascertain with certainty which monitor was used, we have decided to report that data point with this disclaimer. At the 4 h mark, dose rate readings were substantially lower than those typically measured from iodine-131 patients. Table 4 summarizes these results: the highest recorded reading from a Lu-177 octreotate patient at 4 h was below the lowest dose rate reading from an iodine131 therapy patient. The distribution of the two sets of dose rate readings was compared using the Wilcoxon rank-sum test for independent samples, with a resulting P-value below 0.01. Cumulative dose readings were also low, with most radiation measurements registering below the minimum
reportable quantity of 0.03 mSv. Such readings were recorded as an asterisk (*) in Tables 5 and 6. For the initial set of cumulative dose measurements listed in Table 5, a single individual, patient 8, accounted for the majority of recordable readings. Six of the 10 patients did not have a recordable cumulative dose in any device during this time period. In the second time period of cumulative dose readings, all patients but one registered a reportable dose in at least one device, most commonly in the device placed on the lower bed frame. The device on the east wall, located at the head of the patient’s bed and closest to most patients’ livers while sleeping, was the next most likely device to record a measurable dose, which was seen for four of the 10 patients. Once again, the majority of readings listed in this time period were below the minimum recordable dose, as seen in Table 6.
Discussion By both absolute and relative criteria, radiation measurements of Lu-177 octreotate therapy patients yielded dose exposures that would be considered safe by current standards. In moving from an inpatient procedure to an outpatient procedure, the intention is to discharge patients at the 4 h mark rather than at the 20 h mark, thus eliminating the need for overnight isolation. The maximum observed cumulative dose in the 4–20 h time frame was 0.18 mSv, equating to a mean dose rate of 11 μSv/h over that time period, with the vast majority of readings registering well below this level. This maximum was recorded by a device located directly below the patient’s bed, less than 1 m away from the patient resting in that bed. Current Canadian guidelines require that members of the public receive no more than 1 mSv each year, although it permits the primary caregiver of a patient to receive up to 5 mSv annually [15,16]. Yet, even with the maximal observed reading of 11 μSv/h, a caregiver would require over half a month of continual exposure to exceed the safety threshold of 5 mSv, and this calculation discounts any reduction in dose rate due to excretion or radioactive decay of Lu-177. In practice, our Nuclear Medicine Department insists that patients distance
Comparison of aggregate dose rate data between lutetium-177 octreotate therapies and iodine-131 therapies at ∼ 4 h after administration
Table 4
Lutetium-177 octreotate Iodine-131
Sample size (n)
Administered doses (MBq)
Mean (μSv/h)
SD (μSv/h)
Range (μSv/h)
10 10
7400–7550 1870–5785
14.04 103.24
7.7 41.71
(6.8–33) (40–176)
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Lu-177 octreotate radiation exposure Olmstead et al. 133
Table 5
Cumulative radiation dose from commencement of treatment to the 4 h mark
Patient number 1 2 3 4 5 6 7 8 9 10 Largest observed value
Washroom (D1)
West wall (D2)
South wall (D3)
East wall (D4)
* * * * * * * * * * *
* * * * * * * 0.04 0.04 * 0.04
* * * * * * * 0.06 * * 0.06
* * * * * * 0.04 * * * 0.04
North wall (D5) Ceiling (D6) * * * * * * * 0.03 * * 0.03
* * * * * * * 0.04 * * 0.04
Lower bed frame (D7)
Outside door (D8)
* 0.05 * * * * * 0.13 * * 0.13
* * * * * * * * * * *
Lower bed frame (D7)
Outside door (D8)
* 0.04 * 0.05 0.10 0.04 0.04 0.18 0.03 0.14 0.18
* * * * * * * * * * *
Values are in mSv. *Indicates that the reading is below the measureable threshold of 0.03 mSv. Table 6
Cumulative radiation dose from the 4 h mark to the 20 h mark
Patient number 1 2 3 4 5 6 7 8 9 10 Largest observed value
Washroom (D1)
West wall (D2)
South wall (D3)
East wall (D4)
* * * * * * * * * * *
* * * * * * * * * * *
* * 0.03 0.03 * * 0.04 * * * 0.04
* * 0.06 0.03 * 0.04 0.05 * * * 0.06
North wall (D5) Ceiling (D6) * * * * * * * * * 0.04 0.04
* * * 0.07 * * * * * * 0.07
Values are in mSv. *Indicates that the reading is below the measureable threshold of 0.03 mSv.
themselves from others, including the primary caregiver, especially during the initial stages of their treatment. As a result, dose rate readings as high as those observed by the device underneath the patient’s bed are highly unlikely. A more representative cumulative radiation exposure profile would likely be demonstrated by the wallmounted devices. Despite the small dimensions of the room (2.94 × 3.26 m), these devices were significantly farther away from the patient’s bed, at a distance typical of someone in the room with the patient. As expected, the wall-mounted detectors generally recorded lower quantities of radiation exposure than the bed-mounted device because of the additional distance from the patient. Survey meter readings further suggested that Lu-177 octreotate therapies would be safe for caretakers and bystanders if reasonable precautions were taken. In comparison with iodine-131 therapies, Lu-177 octreotate dose rate readings were substantially and reliably lower at the intended time of discharge: the 4 h mark. Lu-177 features a similar physical half-life as iodine-131 but differs with fewer routes of excretion [5,17]. Therefore, it would be reasonable to assume that Lu-177 octreotate outpatient therapy would be safe as well. As additional evidence of the safety of this therapy in an outpatient setting, we can make some fairly unlikely
assumptions and still expect public radiation exposure to remain below our 5 mSv threshold. From Eq. (1) we can estimate the cumulative dose, E, to a person standing a set distance from the patient for an infinite amount of time when only physical decay of Lu-177 is considered. That is, we assume no biological excretion. For simplicity, we will assume a distance of 1 m and will set our initial dose rate reading at that distance, D0, at 20 μSv/h, which is at the high range of our 4 h mark measurements. The half-life of Lu-177, 6.7 days, is represented by t1/2. Upon calculation it can be found that E = 4.6 mSv. Z E¼
1
D0 e lnð2Þt=t1=2 dt:
ð1Þ
0
As stated, the assumptions required to achieve that dose of 4.6 mSv are extremely unlikely to occur in practice. In past experiences with iodine-131 outpatient therapy, caregivers were in close proximity to a post-therapy patient ∼ 25% of the time [17]. Thus, the dose to the caregiver would more likely be ∼ 1.2 mSv before considering biological excretion. Increased biological excretion would further reduce the expected dose, but such excretions also carry a separate radiation risk to others if not properly managed [14]. Iodine-131 outpatients are also expected to account for potential sources of contamination from their excretions,
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134 Nuclear Medicine Communications 2015, Vol 36 No 2
such as using and personally cleaning a private bathroom, using separate eating utensils and plates, as well as washing their clothes and linens separately [14]. As previously stated, Lu-177 octreotate has fewer main routes of biological excretion, with urine and feces being the major sources of potential contamination [9]. Nevertheless, an insistence on using a separate bathroom along with careful washing of soiled linens would be prudent. In comparison with other research, a similar study by Calais and Turner [8] in 2014 indicated higher expected survey meter readings in their analysis of 78 patients, with their findings predicting a mean dose rate at the 4 h mark closer to 18 μSv/h, whereas we observed a mean dose rate closer to 14 μSv/h. However, this value was obtained from a line of best fit created by interpolation from readings taken from just after commencement of therapy until nearly the 6 h mark, with a large majority of readings occurring before the 4 h mark and a significant number occurring less than 1 h after commencement of therapy [8]. As a result, excretion effects may be confounding a direct comparison of our results, which were taken exclusively at the 4 h mark after therapy commenced.
References 1
2
3
4
5 6
7
8
9
10
11
Conclusion With favorable physical and biological characteristics, Lu-177 octreotate would be an excellent candidate for outpatient radioisotope therapy. Lu-177 has a low abundance of γ-ray emissions and fewer routes of biological excretion compared with radioiodine, and the therapy is generally well tolerated by patients with neuroendocrine diseases. This study shows that the radiation exposure to primary caregivers would be well below the threshold of 5 mSv and, from a radiation safety perspective, an outpatient protocol is feasible.
12
13
14
15
16
Acknowledgements Conflicts of interest
There are no conflicts of interest.
17
Culler MD, Oberg K, Arnold R, Krenning EP, Sevilla I, Díaz JA. Somatostatin analogs for the treatment of neuroendocrine tumors. Cancer Metastasis Rev 2011; 30 (Suppl 1):9–17. Kam BL, Teunissen JJ, Krenning EP, de Herder WW, Khan S, van Vliet EI, Kwekkeboom DJ. Lutetium-labelled peptides for therapy of neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2012; 39 (Suppl 1):S103–S112. Bodei L, Cremonesi M, Ferrari M, Pacifici M, Grana CM, Bartolomei M, et al. Long-term evaluation of renal toxicity after peptide receptor radionuclide therapy with 90Y-DOTATOC and 177Lu-DOTATATE: the role of associated risk factors. Eur J Nucl Med Mol Imaging 2008; 35:1847–1856. Kwekkeboom DJ, de Herder WW, Kam BL, van Eijck CH, van Essen M, Kooij PP, et al. Treatment with the radiolabeled somatostatin analog [177Lu-DOTA 0,Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol 2008; 26:2124–2130. Turner JH. Outpatient therapeutic nuclear oncology. Ann Nucl Med 2012; 26:289–297. Perla RJ, Hohmann SF, Annis K. Whole-patient measure of safety: using administrative data to assess the probability of highly undesirable events during hospitalization. J Healthc Qual 2013; 35:20–31. Hassan M, Tuckman HP, Patrick RH, Kountz DS, Kohn JL. Hospital length of stay and probability of acquiring infection. Int J Pharm Healthc Market 2010; 4:324–338. Calais PJ, Turner JH. Radiation safety of outpatient 177Lu-octreotate radiopeptide therapy of neuroendocrine tumors. Ann Nucl Med 2014; 28:531–539. Kwekkeboom DJ, Bakker WH, Kooij PP, Konijnenberg MW, Srinivasan A, Erion JL, et al. [177Lu-DOTAOTyr3]octreotate: comparison with [111InDTPAo]octreotide in patients. Eur J Nucl Med 2001; 28:1319–1325. Bé M, Chisté V, Dulieu C, Browne E, Chechev V, Kuzmanko N, et al. Table of radionuclides. Monographie BIPM-5. Bureau International des Poids et Mesures, 2004; pp:1–150. Bé M, Chisté V, Dulieu C, Browne E, Chechev V, Kuzmanko N, et al. Table of radionuclides. Monographie BIPM-5. Bureau International des Poids et Mesures, 2004; pp:151–242. Bakker WH, Breeman WA, Kwekkeboom DJ, de Jong LC, Krenning EP. Practical aspects of peptide receptor radionuclide therapy with [177Lu] [DOTA0, Tyr3]octreotate. Q J Nucl Med Mol Imaging 2006; 50:265–271. Willegaignon J, Sapienza M, Ono C, Watanabe T, Guimarães MI, Gutterres R, et al. Outpatient radioiodine therapy for thyroid cancer: a safe nuclear medicine procedure. Clin Nucl Med 2011; 36:440–445. Sisson JC, Freitas J, McDougall IR, Dauer LT, Hurley JR, Brierley JD, et al. American Thyroid Association Taskforce On Radioiodine Safety. Radiation safety in the treatment of patients with thyroid diseases by radioiodine 131I : practice recommendations of the American Thyroid Association. Thyroid 2011; 21:335–346. Marriott CJ, Webber CE, Gulenchyn KY. Radiation exposure for ‘caregivers’ during high-dose outpatient radioiodine therapy. Radiat Prot Dosimetry 2007; 123:62–67. Canadian Nuclear Safety Commission. Proposals to amend the Radiation Protection Regulations: discussion paper DIS-13-01. Ottawa: Canadian Nuclear Safety Commission; 2013. Panzegrau B, Gordon L, Goudy GH. Outpatient therapeutic 131I for thyroid cancer. J Nucl Med Technol 2005; 33:28–30.
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Quantifying public radiation exposure related to lutetium-177 octreotate therapy for the development of a safe outpatient treatment protocol Craig Olmsteada, Kyle Cruza, Robert Stodilkaa,b,c, Pamela Zabela,b,c and Robert Wolfsona Objectives Radionuclide therapies, including treatment of neuroendocrine tumors with lutetium-177 (Lu-177) octreotate, often involve hospital admission to minimize radiation exposure to the public. Overnight admission due to Lu-177 octreotate therapy incurs additional cost for the hospital and is an inconvenience for the patient. This study endeavors to characterize the potential radiation risk to caregivers and the public should Lu-177 octreotate therapies be performed on an outpatient basis.
Conclusion Given the low dose rate and cumulative levels of radiation measured, the results support that an outpatient Lu-177 octreotate treatment protocol would not jeopardize public safety. Nevertheless, the concept of ALARA still requires that detailed radiation safety protocols be developed for Lu-177 octreotate outpatients to minimize radiation exposure to family members, caregivers, and the general public. Nucl Med Commun 36:129–134 © 2015 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Materials and methods Dose rate measurements of radiation emanating from 10 patients were taken 30 min, 4, and 20 h after initiation of Lu-177 octreotate therapy. Instadose radiation dose measurement monitors were also placed around the patients’ rooms to assess the potential cumulative radiation exposure during the initial 30 min–4 h after treatment (simulating the hospital-based component of the outpatient model) as well as 4–20 h after treatment (simulating the discharged outpatient portion).
Nuclear Medicine Communications 2015, 36:129–134 Keywords: dosimetry, lutetium-177 octreotate, neuroendocrine tumors, peptide receptor radionuclide therapy, radiation a Department of Nuclear Medicine, London Health Sciences Centre, Victoria Campus, bDepartment of Medical Imaging, Western University and cLawson Health Research Institute, London, Ontario, Canada
Correspondence to Craig Olmstead, BMath, BSc, 298 Wortley Road, London, ON, Canada N6C 3R5 Tel: + 1 519 933 9101; fax: + 1 519 685 8500; e-mail: [email protected]
Results The mean recorded dose rate at 30 min, 4, and 20 h after therapy was 20.4, 14.0, and 6.6 μSv/h, respectively. The majority of the cumulative dose readings were below the minimum recordable threshold of 0.03 mSv, with a maximum dose recorded of 0.18 mSv.
Received 8 August 2014 Revised 22 September 2014 Accepted 23 September 2014
Introduction
surface, particularly SSTR-2, making them an ideal target for delivery of Lu-177 octreotate radiotherapy [2].
The conventional approach to oncologic management typically involves surgery, chemotherapy, and/or external-beam radiation therapy. Recent innovation in the field of molecular target-based therapy has advanced cancer care by tailoring patient treatment to the tumor’s unique cellular blueprints. Peptide receptor radionuclide therapy is one such class of modern molecular therapeutics; by targeting tumors that overexpress a specific receptor, a systemic therapy can be delivered in a more concentrated manner to the tumor with lower exposure to the native cells, thereby maximizing therapeutic delivery while minimizing toxicity to healthy tissue. The peptide receptor radionuclide therapy agent lutetium177 (Lu-177) octreotate is a radiolabelled somatostatin analog that binds preferentially to somatostatin transmembrane receptor (SSTR)-2, as well as to SSTR-3 and SSTR-5, although with weaker affinity [1]. Neuroendocrine tumors classically overexpress somatostatin receptors on their cell 0143-3636 © 2015 Wolters Kluwer Health | Lippincott Williams & Wilkins
Lu-177 octreotate treatment demonstrated therapeutic effectiveness by achieving complete remission, partial remission, or a minor response in 46% of patients [2]. The treatment is generally well tolerated, with patients most commonly exhibiting minor side effects such as hair thinning, nausea, vomiting, and abdominal discomfort [2]. Organ toxicity is uncommon; less than 10% of patients experience subacute hematological toxicity during the course of treatment, and overall rates of renal toxicity are similarly low [2,3]. In a standard course of consolidation treatment at London Health Sciences Centre, patients receive three to four doses of Lu-177 octreotate, administering between 5.7 and 7.4 GBq of activity, with successive therapies performed 2–3 months apart [4]. By way of its γ emissions, Lu-177 radiation exposure is a concern for those who may be in close proximity to the patient, particularly on the DOI: 10.1097/MNM.0000000000000232
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130 Nuclear Medicine Communications 2015, Vol 36 No 2
first day of treatment [5]. As a result of the substantial quantity of Lu-177 octreotate involved with the treatment, current practices in Canada require patients to be isolated in a lead-lined room for their first night after each dose administration to protect others from unnecessary radiation exposure. The required isolation is expensive and, for most patients, not medically warranted. Lu-177 octreotate therapy carries a considerable per-patient cost before including those associated with hospital admission; hence, money-saving measures are important to ensure its cost-effectiveness and therefore its continued availability for patients. The economic imperative to minimize costs is ever-present, and the current economic climate of tightened healthcare budgets only serves to reinforce this necessity. Furthermore, the inpatient model is overly restrictive on the large subset of highly functioning, otherwise healthy, patients who have to endure potentially unnecessary physical and emotional seclusion outside of their home. In addition, an overnight hospital stay increases the patient’s risk for nosocomial infections [6,7]. One study estimated the increased risk of developing a hospital-acquired infection from an additional day in hospital at 1.37% [7]. For these reasons, we have chosen to explore the possibility of eliminating the requirement for full-day isolation by demonstrating that the radiation exposure to others can be safely and effectively managed outside of the hospital setting. Currently, most treatment centers providing Lu-177 octreotate therapy do so only on an inpatient basis, with regulatory differences related to radiation exposure to the public being the primary constraint on how soon a patient undergoing therapy may be discharged from the hospital [5]. For example, in Germany, where more strict radiation regulations exist, patients who receive Lu-177 therapy may be admitted for periods lasting longer than one night, as opposed to those receiving treatment in Australia where less stringent radiation safety requirements allow for an outpatient protocol [5]. Additional work by Calais and Turner [8] in Australia has further supported the acceptability of Lu-177 octreotate therapy on an outpatient basis within that jurisdiction. In addition, dose rate measurements from patients in the Calais and Turner [8] study suggest that outpatient therapy may be feasible within Canada’s regulatory framework. Yet, even in many jurisdictions with lighter regulations, treatment centers often err on the side of caution, resulting in overnight hospital admissions in the absence of rigorous radiation exposure data. Lu-177 octreotate has favorable physical and biological properties in terms of minimizing radiation exposure to the public. The radioisotope undergoes beta decay to emit a low-to-medium-energy β particle, which is predominantly absorbed within the body of the patient, as well as γ-ray emissions of low abundance and low-to-
medium energy, thus minimizing the irradiation of nearby bystanders [5]. The biological excretion for Lu-177 is primarily through the urine and feces, which, for most patients, are easily contained and properly disposed [9]. By comparison, iodine-131, which is used in the treatment of differentiated thyroid carcinoma, has a considerably higher abundance of γ emissions and higher energy gamma rays relative to Lu-177, as seen in Table 1, resulting in a substantially higher specific γ coefficient [10–12]. It also has more routes of biologic excretion, including saliva and sweat [5,13,14]. Radioactive iodine therapies are performed on an outpatient basis at many treatment centers in Canada [15,] and we postulate that the radiation exposure to the public from Lu-177 octreotate outpatient therapy would be less than iodine-131. This article outlines the efforts undertaken at the London Health Sciences Centre’s Victoria campus to quantify the potential levels of public radiation exposure from Lu-177 octreotate therapy for the purpose of establishing the safety of an outpatient protocol.
Materials and methods This study analyzed the radiation emanating from Lu177 octreotate in patients treated at the London Health Sciences Centre. Inclusion criteria for study participation included all of the following: (a) an upcoming Lu-177 octreotate therapy at our institution; (b) an age of at least 18 years with capacity to consent to the research study; (c) ability to comply with the 20 h isolation rules within their designated hospital room; and (d) ability to comply with not tampering with the radiation detector devices utilized in the study. A total of 10 patients were approached to participate in the study, with all potential research subjects agreeing to be involved. The dose administered to these patients ranged between 7400 and 7550 MBq. Ethics approval for this study was granted by The University of Western Ontario Research Ethics Board for Health Sciences Research Involving Human Subjects. Radiation exposure was measured in two ways. First, dose rate measurements using a precalibrated Victoreen 450B-DE-SI (Victoreen, Cleveland, Ohio, USA), recorded in μSv/h were taken at 30 min, 4, and 20 h after infusion of Lu-177 octreotate. These time points were chosen because of their significance in converting the Table 1
Physical characteristics of iodine-131 and lutetium-177
Isotope
Half-life (days)
Iodine-131
8.02
Lutetium-177
6.65
γ emissions (energy) (keV)
γ emissions (abundance) (%)
284 364 642 113 208
6.1 81.2 7.3 6.2 10.4
Specific γ constant (μSv·m2/MBq·h) 0.063
0.0066
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Lu-177 octreotate radiation exposure Olmstead et al. 131
current inpatient protocol to an outpatient one. At 30 min, the patient voids for the first time after the Lu177 octreotate is administered and eliminates a significant quantity of radioactivity through the urine [9]. Because of the high amount of initial excretion, the postvoid reading was considered the more reliable and useful starting point of radiation measurement, especially when extrapolating through the remainder of the therapy. In addition, the patient is isolated during those initial 30 min, eliminating the possibility of exposure to others. The second and third measurement times, at 4 and 20 h, respectively, represent the intended time of discharge with an outpatient protocol and the current discharge time with an inpatient protocol. Each dose rate measurement was taken at a distance of 1 m away from the patient, at the level of the patient’s liver. In addition, direct ion technology dose measurements were obtained within and around the patient’s room to simulate cumulative radiation exposure to family members, caregivers, and the general public. These readings, in mSv, were collected over two time periods: at commencement of therapy until the 4 h mark and from the 4 h mark until the 20 h mark. To obtain these cumulative dose measurements, devices were set up in strategic locations throughout the patient’s room while undergoing treatment. There were eight locations: outside the room’s door, on the wall behind the toilet, above the patient’s bed (mounted to the ceiling), beneath the patient’s bed, and one on each wall within the room. Figures 1 and 2 provide a representative plan of the patient’s room with the location of each detector, and Table 2 details the distance from the center of the patient’s bed to each detector. The direct ion technology devices used for cumulative radiation measurements were Instadose pocket dosimeters (Mirion Technologies, San Ramon, California, USA). These dosimeters can register cumulative radiation doses as low as 0.03 mSv. The Instadose dosimeters were tested for linearity and constancy with a Lu-177 point source before being used in this study. Constancy, evaluated using the 16 devices employed in the study placed 1 m away from a 3.26 GBq source (at the time of initiation) for 2 h, resulted in a mean recorded dose of 0.11 mSv and a SD of 0.012 mSv. To determine the radiation-related safety of Lu-177 octreotate, measurements were analyzed against both absolute and relative standards of safety. For this study, our threshold for safety was 5 mSv/year for the patient’s primary caregiver [16], which is similar to current iodine131 outpatient therapies. Data on 10 iodine-131 therapies were drawn at random from deidentified radiation safety records at the London Health Sciences Centre, which are acquired as part of routine radiation decommissioning practice when performing iodine-131 outpatient therapies (1870–5785 MBq).
Fig. 1
D1 Toilet
Door to washroom D2 Chair
Bed M
D3
D5
D4 D8 Door to hallway Floor diagram of the patient’s room. D1, washroom; D2, west wall; D3, south wall; D4, east wall; D5, north wall; D8, outside door. M indicates the middle of the patient’s bed.
Fig. 2
Ceiling D6
M Bed D7 Floor Cross-section of the patient’s room. D6, ceiling; D7, lower bed frame. M indicates the middle of the patient’s bed.
Results As shown in Table 3, the measured dose rate values generally decreased over time as the activity of intravenously
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132 Nuclear Medicine Communications 2015, Vol 36 No 2
Table 2
Distance between the center of the patient’s bed and cumulative dose detectors
Distance from center of patient’s bed (m)
Table 3
Washroom (D1)
West wall (D2)
South wall (D3)
East wall (D4)
North wall (D5)
Ceiling (D6)
Lower bed frame (D7)
Outside door (D8)
3.83
1.24
1.98
1.88
1.17
1.47
0.56
2.54
Survey meter dose rate readings
Patient number 1 2 3 4 5 6 7 8 9 10 Largest observed value
30 min (postvoid)
4 h mark
Discharge
18.1 18.6 24 24 16.5 18.6 19 22 21 22 24
9.2 9.5 14.2 20 8.8 6.8 33a 10.7 15.5 12.7 33
3.1 1.8 7.2 20 7.5 4.4 11 3.6 4.3 3 20
Values are in μSv/h. Potentially erroneous reading; see the text for full discussion.
a
infused Lu-177 octreotate was progressively eliminated from the body. There were two exceptions to this general trend of decline. First, the dose rate from patient 4 did not drop after the 4 h mark but remained constant at 20 μSv/h at the 20 h mark; the finding can be explained by the high degree of somatostatin-avid tumor burden within this patient, resulting in high trapping rates and minimal biological excretion. Second, the dose rate from patient 7 increased at the 4 h mark when compared with the 30 min mark, but declined substantially by the 20 h mark. The 4 h dose rate reading for patient 7 is suspected to be erroneous; it was discovered after-the-fact that a similar but improperly calibrated monitor may have been used for that lone reading. However, as we have been unable to ascertain with certainty which monitor was used, we have decided to report that data point with this disclaimer. At the 4 h mark, dose rate readings were substantially lower than those typically measured from iodine-131 patients. Table 4 summarizes these results: the highest recorded reading from a Lu-177 octreotate patient at 4 h was below the lowest dose rate reading from an iodine131 therapy patient. The distribution of the two sets of dose rate readings was compared using the Wilcoxon rank-sum test for independent samples, with a resulting P-value below 0.01. Cumulative dose readings were also low, with most radiation measurements registering below the minimum
reportable quantity of 0.03 mSv. Such readings were recorded as an asterisk (*) in Tables 5 and 6. For the initial set of cumulative dose measurements listed in Table 5, a single individual, patient 8, accounted for the majority of recordable readings. Six of the 10 patients did not have a recordable cumulative dose in any device during this time period. In the second time period of cumulative dose readings, all patients but one registered a reportable dose in at least one device, most commonly in the device placed on the lower bed frame. The device on the east wall, located at the head of the patient’s bed and closest to most patients’ livers while sleeping, was the next most likely device to record a measurable dose, which was seen for four of the 10 patients. Once again, the majority of readings listed in this time period were below the minimum recordable dose, as seen in Table 6.
Discussion By both absolute and relative criteria, radiation measurements of Lu-177 octreotate therapy patients yielded dose exposures that would be considered safe by current standards. In moving from an inpatient procedure to an outpatient procedure, the intention is to discharge patients at the 4 h mark rather than at the 20 h mark, thus eliminating the need for overnight isolation. The maximum observed cumulative dose in the 4–20 h time frame was 0.18 mSv, equating to a mean dose rate of 11 μSv/h over that time period, with the vast majority of readings registering well below this level. This maximum was recorded by a device located directly below the patient’s bed, less than 1 m away from the patient resting in that bed. Current Canadian guidelines require that members of the public receive no more than 1 mSv each year, although it permits the primary caregiver of a patient to receive up to 5 mSv annually [15,16]. Yet, even with the maximal observed reading of 11 μSv/h, a caregiver would require over half a month of continual exposure to exceed the safety threshold of 5 mSv, and this calculation discounts any reduction in dose rate due to excretion or radioactive decay of Lu-177. In practice, our Nuclear Medicine Department insists that patients distance
Comparison of aggregate dose rate data between lutetium-177 octreotate therapies and iodine-131 therapies at ∼ 4 h after administration
Table 4
Lutetium-177 octreotate Iodine-131
Sample size (n)
Administered doses (MBq)
Mean (μSv/h)
SD (μSv/h)
Range (μSv/h)
10 10
7400–7550 1870–5785
14.04 103.24
7.7 41.71
(6.8–33) (40–176)
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Lu-177 octreotate radiation exposure Olmstead et al. 133
Table 5
Cumulative radiation dose from commencement of treatment to the 4 h mark
Patient number 1 2 3 4 5 6 7 8 9 10 Largest observed value
Washroom (D1)
West wall (D2)
South wall (D3)
East wall (D4)
* * * * * * * * * * *
* * * * * * * 0.04 0.04 * 0.04
* * * * * * * 0.06 * * 0.06
* * * * * * 0.04 * * * 0.04
North wall (D5) Ceiling (D6) * * * * * * * 0.03 * * 0.03
* * * * * * * 0.04 * * 0.04
Lower bed frame (D7)
Outside door (D8)
* 0.05 * * * * * 0.13 * * 0.13
* * * * * * * * * * *
Lower bed frame (D7)
Outside door (D8)
* 0.04 * 0.05 0.10 0.04 0.04 0.18 0.03 0.14 0.18
* * * * * * * * * * *
Values are in mSv. *Indicates that the reading is below the measureable threshold of 0.03 mSv. Table 6
Cumulative radiation dose from the 4 h mark to the 20 h mark
Patient number 1 2 3 4 5 6 7 8 9 10 Largest observed value
Washroom (D1)
West wall (D2)
South wall (D3)
East wall (D4)
* * * * * * * * * * *
* * * * * * * * * * *
* * 0.03 0.03 * * 0.04 * * * 0.04
* * 0.06 0.03 * 0.04 0.05 * * * 0.06
North wall (D5) Ceiling (D6) * * * * * * * * * 0.04 0.04
* * * 0.07 * * * * * * 0.07
Values are in mSv. *Indicates that the reading is below the measureable threshold of 0.03 mSv.
themselves from others, including the primary caregiver, especially during the initial stages of their treatment. As a result, dose rate readings as high as those observed by the device underneath the patient’s bed are highly unlikely. A more representative cumulative radiation exposure profile would likely be demonstrated by the wallmounted devices. Despite the small dimensions of the room (2.94 × 3.26 m), these devices were significantly farther away from the patient’s bed, at a distance typical of someone in the room with the patient. As expected, the wall-mounted detectors generally recorded lower quantities of radiation exposure than the bed-mounted device because of the additional distance from the patient. Survey meter readings further suggested that Lu-177 octreotate therapies would be safe for caretakers and bystanders if reasonable precautions were taken. In comparison with iodine-131 therapies, Lu-177 octreotate dose rate readings were substantially and reliably lower at the intended time of discharge: the 4 h mark. Lu-177 features a similar physical half-life as iodine-131 but differs with fewer routes of excretion [5,17]. Therefore, it would be reasonable to assume that Lu-177 octreotate outpatient therapy would be safe as well. As additional evidence of the safety of this therapy in an outpatient setting, we can make some fairly unlikely
assumptions and still expect public radiation exposure to remain below our 5 mSv threshold. From Eq. (1) we can estimate the cumulative dose, E, to a person standing a set distance from the patient for an infinite amount of time when only physical decay of Lu-177 is considered. That is, we assume no biological excretion. For simplicity, we will assume a distance of 1 m and will set our initial dose rate reading at that distance, D0, at 20 μSv/h, which is at the high range of our 4 h mark measurements. The half-life of Lu-177, 6.7 days, is represented by t1/2. Upon calculation it can be found that E = 4.6 mSv. Z E¼
1
D0 e lnð2Þt=t1=2 dt:
ð1Þ
0
As stated, the assumptions required to achieve that dose of 4.6 mSv are extremely unlikely to occur in practice. In past experiences with iodine-131 outpatient therapy, caregivers were in close proximity to a post-therapy patient ∼ 25% of the time [17]. Thus, the dose to the caregiver would more likely be ∼ 1.2 mSv before considering biological excretion. Increased biological excretion would further reduce the expected dose, but such excretions also carry a separate radiation risk to others if not properly managed [14]. Iodine-131 outpatients are also expected to account for potential sources of contamination from their excretions,
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134 Nuclear Medicine Communications 2015, Vol 36 No 2
such as using and personally cleaning a private bathroom, using separate eating utensils and plates, as well as washing their clothes and linens separately [14]. As previously stated, Lu-177 octreotate has fewer main routes of biological excretion, with urine and feces being the major sources of potential contamination [9]. Nevertheless, an insistence on using a separate bathroom along with careful washing of soiled linens would be prudent. In comparison with other research, a similar study by Calais and Turner [8] in 2014 indicated higher expected survey meter readings in their analysis of 78 patients, with their findings predicting a mean dose rate at the 4 h mark closer to 18 μSv/h, whereas we observed a mean dose rate closer to 14 μSv/h. However, this value was obtained from a line of best fit created by interpolation from readings taken from just after commencement of therapy until nearly the 6 h mark, with a large majority of readings occurring before the 4 h mark and a significant number occurring less than 1 h after commencement of therapy [8]. As a result, excretion effects may be confounding a direct comparison of our results, which were taken exclusively at the 4 h mark after therapy commenced.
References 1
2
3
4
5 6
7
8
9
10
11
Conclusion With favorable physical and biological characteristics, Lu-177 octreotate would be an excellent candidate for outpatient radioisotope therapy. Lu-177 has a low abundance of γ-ray emissions and fewer routes of biological excretion compared with radioiodine, and the therapy is generally well tolerated by patients with neuroendocrine diseases. This study shows that the radiation exposure to primary caregivers would be well below the threshold of 5 mSv and, from a radiation safety perspective, an outpatient protocol is feasible.
12
13
14
15
16
Acknowledgements Conflicts of interest
There are no conflicts of interest.
17
Culler MD, Oberg K, Arnold R, Krenning EP, Sevilla I, Díaz JA. Somatostatin analogs for the treatment of neuroendocrine tumors. Cancer Metastasis Rev 2011; 30 (Suppl 1):9–17. Kam BL, Teunissen JJ, Krenning EP, de Herder WW, Khan S, van Vliet EI, Kwekkeboom DJ. Lutetium-labelled peptides for therapy of neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2012; 39 (Suppl 1):S103–S112. Bodei L, Cremonesi M, Ferrari M, Pacifici M, Grana CM, Bartolomei M, et al. Long-term evaluation of renal toxicity after peptide receptor radionuclide therapy with 90Y-DOTATOC and 177Lu-DOTATATE: the role of associated risk factors. Eur J Nucl Med Mol Imaging 2008; 35:1847–1856. Kwekkeboom DJ, de Herder WW, Kam BL, van Eijck CH, van Essen M, Kooij PP, et al. Treatment with the radiolabeled somatostatin analog [177Lu-DOTA 0,Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol 2008; 26:2124–2130. Turner JH. Outpatient therapeutic nuclear oncology. Ann Nucl Med 2012; 26:289–297. Perla RJ, Hohmann SF, Annis K. Whole-patient measure of safety: using administrative data to assess the probability of highly undesirable events during hospitalization. J Healthc Qual 2013; 35:20–31. Hassan M, Tuckman HP, Patrick RH, Kountz DS, Kohn JL. Hospital length of stay and probability of acquiring infection. Int J Pharm Healthc Market 2010; 4:324–338. Calais PJ, Turner JH. Radiation safety of outpatient 177Lu-octreotate radiopeptide therapy of neuroendocrine tumors. Ann Nucl Med 2014; 28:531–539. Kwekkeboom DJ, Bakker WH, Kooij PP, Konijnenberg MW, Srinivasan A, Erion JL, et al. [177Lu-DOTAOTyr3]octreotate: comparison with [111InDTPAo]octreotide in patients. Eur J Nucl Med 2001; 28:1319–1325. Bé M, Chisté V, Dulieu C, Browne E, Chechev V, Kuzmanko N, et al. Table of radionuclides. Monographie BIPM-5. Bureau International des Poids et Mesures, 2004; pp:1–150. Bé M, Chisté V, Dulieu C, Browne E, Chechev V, Kuzmanko N, et al. Table of radionuclides. Monographie BIPM-5. Bureau International des Poids et Mesures, 2004; pp:151–242. Bakker WH, Breeman WA, Kwekkeboom DJ, de Jong LC, Krenning EP. Practical aspects of peptide receptor radionuclide therapy with [177Lu] [DOTA0, Tyr3]octreotate. Q J Nucl Med Mol Imaging 2006; 50:265–271. Willegaignon J, Sapienza M, Ono C, Watanabe T, Guimarães MI, Gutterres R, et al. Outpatient radioiodine therapy for thyroid cancer: a safe nuclear medicine procedure. Clin Nucl Med 2011; 36:440–445. Sisson JC, Freitas J, McDougall IR, Dauer LT, Hurley JR, Brierley JD, et al. American Thyroid Association Taskforce On Radioiodine Safety. Radiation safety in the treatment of patients with thyroid diseases by radioiodine 131I : practice recommendations of the American Thyroid Association. Thyroid 2011; 21:335–346. Marriott CJ, Webber CE, Gulenchyn KY. Radiation exposure for ‘caregivers’ during high-dose outpatient radioiodine therapy. Radiat Prot Dosimetry 2007; 123:62–67. Canadian Nuclear Safety Commission. Proposals to amend the Radiation Protection Regulations: discussion paper DIS-13-01. Ottawa: Canadian Nuclear Safety Commission; 2013. Panzegrau B, Gordon L, Goudy GH. Outpatient therapeutic 131I for thyroid cancer. J Nucl Med Technol 2005; 33:28–30.
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