Radioactivity of Blood Samples Taken from Thyroidectomized Thyroid Carcinoma Patients After Therapy with 131 I

Abstract

Background:

Occasionally, blood samples may be required from thyroid cancer patients after they have been given the therapy dose of ¹³¹I, as part of necessary medical management of comorbidities. Thus, in the days after ¹³¹I administration, medical health professionals may be involved in the withdrawal, handling, and manipulation of radioactive blood samples. The purpose of this study was to quantify the amount of radioactivity in blood samples taken from thyroidectomized thyroid carcinoma patients after the administration of therapeutic activities of ¹³¹I.

Methods:

For dosimetry purposes, serial blood sampling is performed on thyroidectomized thyroid carcinoma patients prior to therapy with ¹³¹I. The quantities of radioactive material present in these blood samples were expressed as a percentage of the administered activity and then extrapolated to the high levels of ¹³¹I used in therapy for 377 patients in this study. The corresponding radiation exposure rate from the blood samples was then calculated to determine what radiation protection methods were required for staff handling these samples.

Results:

The average amount of radioactivity in a 1 mL blood sample at 1 hour postadministration of 5.5 GBq (150 mCi) of ¹³¹I was 0.2 ± 0.15 MBq (5.4 ± 4.0 μCi). This corresponds to an exposure rate of 1.23 μSv/h (0.123 mrem/h) at 10 cm from the sample. For samples obtained beyond 24 hours after a therapeutic administration of 5.55 GBq (150 mCi), the exposure levels are approximately equal to background radiation.

Conclusion:

The data in this study indicate that the radiation exposure from blood samples withdrawn from thyroidectomized thyroid cancer patients is low. However, to ensure that staff members are exposed to minimal levels of radiation, it is imperative that staff members who are involved in withdrawing, handling, or manipulating radioactive blood samples adhere to the recommended radiation safety practices.

Introduction

A djuvant therapy of differentiated thyroid cancer with radioactive iodine is a standard procedure for the ablation of remnant thyroid tissue following surgery and for the treatment of iodine-avid metastases (1). ¹³¹I is a high-energy gamma and beta emitter with a physical half-life of 8.01 days (2). Because of its long half-life and the retention of ¹³¹I by thyroid remnants, patients will act as a source of radiation exposure to those who are in contact with them or their bodily fluids for several days after they have been administered radioactive ¹³¹I. Therefore, it is common practice to isolate these patients at home or in a hospital and to avoid testing their fluids such as blood and urine. However, occasionally, blood samples may be required from thyroid cancer patients after they have been given the therapy dose of ¹³¹I, as part of necessary medical management, especially when there are comorbidities. Thus, in the days after ¹³¹I administration, medical health professionals may be involved in the withdrawal, handling, and manipulation of radioactive blood samples. This invariably leads to questions and concerns regarding the level of radiation exposure involved, particularly from staff members who do not routinely deal with radiation, such as physicians, phlebotomists, nurses, and laboratory staff (e.g., biochemistry, hematology, or immunology).

Prior to ¹³¹I therapy, the presence and extent of iodine-accumulating thyroid tissue is determined by uptake measurement and imaging (3,4). In this center, most thyroidectomized thyroid cancer patients undergo a radioactive iodine uptake test, which involves serial measurements of the patient's whole-body activity using a calibrated probe and a whole-body scan at selected times after administration of a tracer amount of ¹³¹I (1–2 mCi). In addition, to permit dosimetry calculations, serial blood sampling is also preformed. The data gathered in this procedure enable the performance of patient-specific dosimetry based on the bone marrow dose-limited approach (5,6). This dosimetry methodology allows an estimate to be calculated for the radiation dose that will be delivered to the hematopoietic system for each GBq administered to the patient. The basis of this approach is that the amount of radioactivity present in aliquots of blood obtained after the administration of a tracer amount of ¹³¹I can be expressed as a fraction of the administered activity and extrapolated to the higher levels of activity used in therapy. Employing the same principle, the radioactive contents of the blood samples of several pretherapy patients were analyzed to predict the amount of radioactive material present in blood samples taken from patients at various times after the administration of therapeutic activities of ¹³¹I. This allowed us to calculate the radiation exposure levels the staff members in contact with the sample would be exposed to. From this we determined whether the current radiation safety instructions provided to nurses, technicians, and physicians were appropriate or whether additional radiation safety guidelines were required.

Materials and Methods

The amount of ¹³¹I retained in the body and hence in the blood samples is determined by the patient-specific kinetics and the degree of thyroid tissue present. The level of ¹³¹I reduces over time in the patient and hence in the blood samples. The rate of reduction is governed by the effective half-life, which is determined by the physical and biological (patient specific) decay rates. In accordance with the bone marrow dosimetry approach, aliquots of herparinized blood samples are obtained at 1, 4, 24, and 48 hours after the administration of a tracer amount of ¹³¹I for each patient. If further clearance data are required for clinical purposes, additional blood samples are also withdrawn at 72 and/or 96 hours. All blood samples are stored until the last sample has been collected.

Once collection is complete, the activity in the blood is determined by assaying 1 mL of each blood sample in an automatic gamma counter. The gamma counter determines the counts per minute (cpm) detected in the sample. In addition, a 1 mL standard of ¹³¹I with known activity is also assayed in the gamma counter. The radioactivity present in the blood sample was determined as follows: \documentclass{aastex}\usepackage{amsbsy}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{bm}\usepackage{mathrsfs}\usepackage{pifont}\usepackage{stmaryrd}\usepackage{textcomp}\usepackage{portland,xspace}\usepackage{amsmath,amsxtra}\pagestyle{empty}\DeclareMathSizes{10}{9}{7}{6} \begin{document} \begin{align*}&\hbox{\rm Amount of radioactivity per CPM (MBq/CPM)} \\& \quad=\hbox{radioactivity in}\ ^{131}{\rm I} \ \hbox{standard(MBq)/} \hbox{\rm CPM} \\ &\qquad \ \hbox{\rm of}\ ^{131}{\rm I} \ \hbox{\rm standard} \tag{1} \end{align*} \end{document} \documentclass{aastex}\usepackage{amsbsy}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{bm}\usepackage{mathrsfs}\usepackage{pifont}\usepackage{stmaryrd}\usepackage{textcomp}\usepackage{portland,xspace}\usepackage{amsmath,amsxtra}\pagestyle{empty}\DeclareMathSizes{10}{9}{7}{6} \begin{document} \begin{align*}&\hbox{Radioactivity in blood sample (MBq)} \\ & \quad= \hbox{CPM of blood sample (CPM)} \ \\ &\quad \times \ \hbox{amount of radioactivity per CMP (MBq/CPM)} \tag{2} \end{align*} \end{document}

The dosimetry method used in this center defines the maximum treatment activity as the amount of ¹³¹I that would deliver an absorbed dose of 2 Gy to the blood compartment (6). The amount of ¹³¹I used to ablate residual thyroid tissue varies over a range of 1.11 GBq (30 mCi) to 3.7 GBq (100 mCi) and the amount required to treat thyroid cancer and distant metastases generally exceeds these amounts several fold (4). The amount of ¹³¹I administered to the patient and the patient's thyroid/tumor uptake will directly impact the amount of radiation exposure from the patient to nearby medical workers and how much radioactivity will be contained in blood samples taken from the patient. The quantity of radioactive material present in blood samples obtained at various times during the tracer test was expressed as a percentage of the administered activity. These values were then extrapolated to determine the amount of activity in the blood samples for the high levels of ¹³¹I used in therapy. Once the activity in a blood sample was determined, the exposure rate that the staff member would be exposed to was calculated using the gamma constant for ¹³¹I of 7.647 × 10⁻⁵ mSv/(h MBq) at 1 m (0.227 mR/[h mCi] at 1 m) (7).

The patients in this study had as near as possible a total thyroidectomy prior to this investigation and therefore had little or no normal thyroid remnant tissue or local or metastatic thyroid cancer producing thyroxine. They were prepared for the tracer whole-body scan with a low-iodine diet regimen and then thyroid-stimulating hormone elevation was secured either by withdrawing thyroid hormone medication or by administering recombinant thyroid-stimulating hormone. The former group of patients was hypothyroid and the latter was euthyroid, because thyroxine was continued. Data from 377 thyroid carcinoma patients were analyzed in this study for blood samples ranging from 1 to 48 hours. This sample size results in a confidence interval (CI) of 95% and a margin of error of 5%. For the later blood samples, fewer patients were available; a sample size of 325 (95% CI, 5.4% margin of error) and 53 were used (95% CI, 13.5% margin of error) for 72 and 96 hours, respectively.

Results

Table 1 displays the percentage of activity measured in a 1 mL blood sample as a function of the administered activity at various times after ¹³¹I administration. The activity in 1 mL of blood as a percentage of the administered activity decreased from 3.6 × 10⁻³% of the administered dose after 1 hour to 0.41 × 10⁻³% after 96 hours. As expected, the amount of radiation present in the blood samples decreases from time since administration. The data from Table 1 can be used to estimate the residual activity in a blood sample once the administered activity and the withdrawal time are known as follows: \documentclass{aastex}\usepackage{amsbsy}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{bm}\usepackage{mathrsfs}\usepackage{pifont}\usepackage{stmaryrd}\usepackage{textcomp}\usepackage{portland,xspace}\usepackage{amsmath,amsxtra}\pagestyle{empty}\DeclareMathSizes{10}{9}{7}{6} \begin{document} \begin{align*}&\hbox{Activity in 1 mL of blood after administration} \ \\& \quad{\hbox{of \it X \rm GBq of}^{131}}{\rm I}=(\% \ \hbox{activity from appropriate} \\ & \quad \hbox{time field from} \ \hbox{\rm Table 1} \times X \ {\rm GBq}/100) \tag{3} \end{align*} \end{document}

Table 1.

The Percentage of Activity Measured in a 1 mL Blood Sample as a Function of the Administered Activity at Various Times After Administration

	Activity in 1 mL blood as a percentage of the administered activity
Time post-administration of ¹³¹I	Average (%)	Standard deviation	No. of patients
1 hour	3.6 × 10⁻³	2.7 × 10⁻³	377
4 hours	2.7 × 10⁻³	1.2 × 10⁻³	377
24 hours	1.1 × 10⁻³	4.8 × 10⁻³	377
48 hours	0.42 × 10⁻³	1.9 × 10⁻³	377
72 hours	0.27 × 10⁻³	1.1 × 10⁻³	325
96 hours	0.41 × 10⁻³	1.3 × 10⁻³	53

For example, an administration of 3.7 GBq (100 mCi) would result in 0.133 MBq (3.6 μCi) in a 1 mL blood sample withdrawn at 1 hour after administration. The exposure rate that the staff member could be exposed to can then be calculated using the gamma constant for ¹³¹I of 2.27 R/(h mCi) at 1 cm.

Table 2 displays the quantity of radioactivity in a 1 mL blood sample at various times after administration of 5.5 GBq (150 mCi) of ¹³¹I, as an example. Exposure levels have been calculated assuming a person was at a distance of 20 cm from the source for 10 minutes. The exposure rate is expressed in μSv/h (mR/h) and also as the equivalent number of minutes of background radiation. It is clear from the results in Table 2 that the radiation exposure from the blood samples is very low, and as expected, the exposure rate decreases in an exponential fashion between 1 hour and 72 hours postadministration. The higher average radiation levels at 96 hours are due to both smaller sample size and also the fact that the patients in this group required additional blood sampling because of their longer retention rates. For samples obtained beyond 24 hours after a therapeutic administration of 5.5 GBq (150 mCi), the exposure levels are approximately equal to background radiation.

Table 2.

The Calculated Quantity of Radioactivity in a 1 mL Blood Sample at Various Times After the Administration of 5.5 GBq (150 mCi) of ¹³¹I

Time postadministration of 150 mCi ¹³¹I	Activity per mL of blood, MBq (μCi)	Average exposure rate at 20 cm from a 4 mL blood sample, μSv/h (mR/h)	Equivalent no. of minutes of background radiation for 10 minutes exposure at 20 cm from the source ^a
1 hour	0.2 ± 0.15 (5.4 ± 4.0)	1.23 (0.123)	29
4 hours	0.15 ± 0.07 (4.1 ± 1.8)	0.93 (0.093)	22
24 hours	0.06 ± 0.26 (1.6 ± 7.2)	0.36 (0.036)	9
48 hours	0.02 ± 0.1 (0.6 ± 2.8)	0.14 (0.014)	3
72 hours	0.01 ± 0.06 (0.4 ± 1.6)	0.09 (0.009)	2
96 hours	0.02 ± 0.07 (0.62 ± 2.0)	0.14 (0.014)	3

Background radiation is taken as 0.01 mSv (1 mrem) per day.

If the blood sample is shielded during transport and storage, the exposure levels to staff members will be significantly reduced. Based on a half value layer of 3 mm Pb for ¹³¹I (7), if a standard shielded syringe carrier (3.2 mm Pb, Biodex) is used to transport or store the sample, it will reduce the exposure rate by approximately 50%. Another effective method of reducing radiation exposure is to maximize the distance from the radioactive sample where possible. Figure 1 displays the effect of distance on reducing the exposure from the radioactive blood sample withdrawn at 1 hour post-administration of 5.5 GBq (150 mCi) ¹³¹I. At a distance of 40 cm from an unshielded source, the exposure level is equivalent to normal background radiation, assuming a background radiation rate of 10 μSv/day (1 mrem/day). Non-radiation workers are subject to the same annual dose limit as a member of the general public of 1 mSv (100 mrem) (8). Assuming no other occupational exposure, a non-radiation worker spending 10 minutes at 20 cm from each sample withdrawn at 1 hour post-administration of 5.5 GBq (150 mCi) of ¹³¹I could work with approximately 4,800 samples before exceeding the regulatory limits.

FIG. 1.

The effect of distance on reducing the exposure from a radioactive blood sample withdrawn at 1 hour after administration of 150 mCi ¹³¹I.

Discussion

The data in this study predict that radiation exposure from blood specimens after therapeutic amounts of ¹³¹I have been administered to thyroidectomized patients with thyroid cancer will be quite low. To minimize staff exposure even further, the universal principles of radiation protection, time, distance, and shielding should be used where appropriate when handling the blood samples.

The patients in this study were thyroidectomized and the uptake of tracer ¹³¹I was generally less than 3%, and in the majority of cases, it was 1% or less. Thus, they produced little if any thyroxine or triiodothyronine. Therefore, the ¹³¹I in blood specimens was almost entirely in the form of inorganic iodide. No patients had renal failure; hence, the inorganic ¹³¹I was rapidly cleared from the body within the first day for the euthyroid ones and by 72 or 96 hours for the hypothyroid patients. Our data and conclusions about radiation exposure from blood specimens are not applicable to patients who have not been thyroidectomized prior to treatment with ¹³¹I or to the very rare thyroid cancer patient who has hyperfunctioning, bulky thyroid metastases. Especially in such hyperthyroid patients, administered therapeutic ¹³¹I will be abundantly converted to radioactive thyroxine, which will remain in the blood much longer than inorganic ¹³¹I and will augment radioactivity with circulating ¹³¹I-labeled thyroxine. We have not assessed the radiation exposure from blood specimens from a patient who is hyperthyroid due to extensive functioning thyroid cancer. However, we anticipate that blood specimens from such a patient may carry a radiation burden that needs to be individually assayed when blood testing is clinically required. It should be noted that our data do not apply to patients with conventional hyperthyroidism such as Graves' disease who are treated with radioactive iodine.

Conclusion

We suggest that the data presented here will serve to provide reasonable estimates of the levels of ¹³¹I to expect in a sample of blood drawn for necessary diagnostic testing from a thyroidectomized thyroid cancer patient at intervals after therapeutic quantities of ¹³¹I were administered. The data also can reassure medical health professionals such as physicians, nurses, lab directors, or RSOs about the associated minimal radiation exposure.

Footnotes

Disclosure Statement

The authors declare that no competing financial interests exist.

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