An indirect high iodine (131I) effective dose used for thyroid ablation in patients with thyroid cancer. Is the method of measurement important?

Abstract Background Radiation effective dose to the red bone‐marrow, a critical organ in the therapy of differentiated thyroid carcinoma (DTC) with radioiodine‐131 (131I), cannot be measured directly. As radioiodine concentration is comparable in blood and most organs, and is believed to be similar in red marrow, the effective dose to the blood seems to be a good first‐order approximation of the radiation effective dose to the hematopoietic system and a better means to quantifying exposure from therapy compared to the total amount of activity administered. Purpose We applied four formulas (Lassmann et al (standard) [2008], Eur J Nucl Med Molecul Imaging, 35:1405–1412), (Thomas et al. [1993], Nucl Med Biol, 20:157–162), (Sisson et al. [2003], J Nucl Med, 44:898–903; Ha¨nscheid et al. [2009], Endocr Relat Cancer, 16:1283–1289) and (Ha¨nscheid et al. [2006], J Nucl Med, 47:648–654) and compared between the estimated values of the effective dose that were obtained by three formulas and those obtained by the standard one. Materials and methods Twenty‐seven patients, 22 women and 5 men, suffering from DTC were enrolled in this study. Whole‐body probe measurements and blood collections (2 mL whole‐blood samples) were conducted at 2, 6, 24, 48, 72–96 h after the administration of 131I to obtain time–activity curves. Whole‐body measurements were performed as conjugate view (anterior and posterior) counts by scintillation camera imaging. Results By comparing the values of blood effective dose that were obtained by applying Thomas et al. [1993], Nucl Med Biol, 20:157–162; Sisson et al. [2003], J Nucl Med, 44:898–903 and Ha¨nscheid et al. [2009], Endocr Relat Cancer, 16:1283–1289, and Ha¨nscheid et al. [2006], J Nucl Med, 47:648–654, techniques, with those obtained by (Lassmann et al (standard technique) [2008], Eur J Nucl Med Molecul Imaging, 35:1405–1412), we found that these values are, respectively, 15.0%, 40.0%, and 41.0% more than those obtained by using the standard method. To our knowledge no papers have been published previously that compare between these dosimetric approaches. Conclusion Highly overestimated or highly underestimated results obtained by a certain method or technique, compared with those obtained by the standard method, are not desirable, they tend to exaggerate in applying radiation protection procedures, by increasing or decreasing, which, in both cases, become far from the realistic or recommended procedures. As an operating philosophy, the objective of radiation safety practices simply should not be to keep radiation doses within legal limits or maximum permissible doses (MPDs), but to keep them “as low as reasonably achievable” (ALARA concept). MPDs should not be considered as thresholds below which exposure to radiation is of no concern, they are not assumed to be totally risk free, and any reasonable technique for reducing radiation dose may have potential benefits in the long run.

method, are not desirable, they tend to exaggerate in applying radiation protection procedures, by increasing or decreasing, which, in both cases, become far from the realistic or recommended procedures. As an operating philosophy, the objective of radiation safety practices simply should not be to keep radiation doses within legal limits or maximum permissible doses (MPD s ), but to keep them "as low as reasonably achievable" (ALARA concept). MPD s should not be considered as thresholds below which exposure to radiation is of no concern, they are not assumed to be totally risk free, and any reasonable technique for reducing radiation dose may have potential benefits in the long run. Radiation exposure from fixed activities is very heterogeneous.
Depending principally on the patient's size and renal clearance, the calculated blood absorbed dose per administered unit of activity can differ by a factor of more than 5. 3 A low absorbed dose to the blood might predict reduced radioiodine availability for target tissue uptake and, therefore, a low absorbed dose to the target tissue. Usually 1.1-3.7 GBq is prescribed for the first radioiodine therapy after thyroidectomy in newly diagnosed DTC patients to ablate the remaining glandular tissue. Higher amounts of 131 I are given in subsequent therapies or in cases of metastatic disease. For safety reasons the activity is usually limited to approximately 7.4 GBq. 3 However, a higher administered activity is usually desired to achieve higher tumor doses. To avoid serious complications, the commonly used dose concept published by Benua et al. 1 for radioiodine treatment of DTC restricts the blood dose to <2 Gy. In their protocol, measurements of iodine retention in the blood and whole body with a tracer activity are required to estimate the blood dose before the radioiodine therapy. This method has been applied successfully. 4,5 Several total body dosimetry formulas in the treatment of DTC have been developed and refined in a series of international multicenter trials, 3,6,7 some of these methods use blood samples, whereas others prefer measuring radiation externally by Geiger Müller or gamma camera. In addition, measurements can be performed at different time intervals.
The aim of this study is to calculate the radiation effective doses in the blood of patients with DTC treated with radioactive iodine using a modified Benua method. To achieve this we employ standard operational procedures (SOP). In addition, we compare between the estimated values obtained by three formulas and those obtained by standard SOP method. To the best of our knowledge, no studies have been published that compare between these dosimetric approaches.

| SUBJECTS, MATERIAL AN D METHOD S
Twenty-seven patients, 22 women, and 5 men, suffering from DTC were recruited for this study. All patients provided informed consent to participate in the study.
The information and data concerning these patients (weight, height, retention function, and residence time), are taken from table 3 in the appendix of Ref. [3].
The data extraction was performed by drawing regions of interest (ROI) at each site according to a dosimetry operational manual with detailed instructions that were distributed to all participating centers before the beginning of the study.
Whole-body probe measurements and blood collections (2 mL whole-blood samples) were conducted 2, 6, 24, 48, 72-96 h after the administration of 131 I to obtain time-activity curves. The "Stan- where τ totalbody is the total body residence time; τ mlofblood is the residence time in a milliliter of whole blood. Finally wt is the patient's weight in kg.
A method to estimate blood dose from external whole-body counting without blood sampling was proposed by Thomas et al. 8 The following equation was applied: Sisson et al. 9 and Ha¨nscheid et al. 10 proposed to use the 48 h whole-body retention measured in a diagnostic assessment to adapt the activity in the subsequent radioiodine therapy in case of markedly low or high 48 h whole-body uptake, and they applied the following formula: The individual blood volume (BLV) can be estimated from the patient's weight wt (kg) and height ht (cm), by applying the following formula that was proposed by Retzlaff et al. 11 : Where BLV = 31.9 × ht + 26.3 × wt − 2402 for males and BLV = 56.9 × ht + 14.1 × wt − 6460 for females.
Furthermore, a blood dose estimate from a single measurement of the whole-body retention can be deduced if the retention R(t) at t hours after the radioiodine administration is taken to be representative for the total-body residence time.
The absorbed dose to the blood was calculated with a modified method deduced from a procedure originally described by Thomas et al. 8 This refined method was applied by Ha¨nscheid et al. 3 They applied the following equation: This technique is based on the formalism by the MIRD Committee of the Society of Nuclear Medicine. Published S values, [12][13][14] were used to account for contributions of activity in the blood and the remainder of the body to the blood dose.
Blood effective dose estimates calculated according to the techniques of Thomas et al. 8 (Sisson et al.,9 Ha¨nscheid et al. 10 ) and Ha¨nscheid et al., 3  The results obtained by applying the Sisson et al. 9 6 The results also show that the values that were calculated by applying the Ha¨nscheid et al. 3 technique are all highly overestimated, which is not realistic, even though they have an excellent correlation (r = 0.99), as shown in Fig. 3 with the standard value.
Highly overestimated or highly underestimated results obtained by a certain method or technique are not desirable, they tend to exaggerate in applying radiation protection procedures, by increasing or decreasing, which, in both cases, become far from the realistic or recommended procedures. We believe that the results obtained using the method of Thomas et al. 8 Table 1.
Our estimated values for specific effective dose (mSv/MBq) and effective dose (mSv) for adult subjects from selected internally administered radiopharmaceuticals are shown in Table 2.

| DISCUSSION
From a historical point of view, it has long been accepted that a single administration of a higher radioiodine level results in a more successful ablation. This was based on the hypothesis that larger levels of radioiodine, are more likely to ablate remnants and destroy residual micrometastases than lower levels. 15 Leila et al. 16   treatment. If a patient has an effective half-life longer than assumed, the patient will receive a higher absorbed dose than planned and be exposed to unnecessary radiation.
With high-dose therapy, the dose to the blood should be W T = 0.12 for blood (bone-marrow). Table 1 shows that there are differences between the values that were obtained from the four methods.
Comparing the values of blood effective dose that were obtained by applying Thomas et al., 8 Sisson et al., 9 Ha¨nscheid et al., 10  In our laboratory, we prefer applying the Thomas et al. 8

| CONCLUSION
From the three methods applied in this research, we believe that the estimated values (results) that are obtained by Thomson et al. 8 are better than those obtained by the other two methods such as Sisson et al., 9 Hänscheid et al. 10 and Hänscheid et al. 3 They are more realistic (66.7% of the cases are overestimated) and have excellent correlation coefficient (r = 90%) compared with those obtained by Lassmann et al. (the standard method) 6 ). Highly overestimated or highly underestimated results obtained by certain methods or techniques, compared with those obtained by the standard method, are not desirable, as they tend to exaggerate in applying radiation protection procedures, by increasing or decreasing, which, in both cases, become far from the realistic or recommended procedures. As an operating strategy or philosophy, the objective of radiation safety practices should not be simply to keep radiation doses within legal limits, but to keep them "as low as reasonably achievable" (ALARA concept).
ACKNOWLEDGMENT I would like to thank Prof. Dr. Abdelatif Alsharif , Nuclear Medicine Section, Radiology and Nuclear Medicine Department, University of Jordan, for critical reading of the manuscript and for his faithful comments.

CONF LICT OF I NTEREST
The author declares that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

FUNDING INFORMATION
This research did not receive any specific grant from any funding agency in the public, commercial, or not-for-profit sector.