**2.2 Imaging timing of RxWBS**

Radioiodine is excreted slowly in hypothyroid patients, especially if they have been on a low iodine diet (Dietlein et al., 2005). Therefore, decreasing background activity is important for visualizing small metastases or remnant thyroid tissue. However, current guidelines for I-131 therapy differ in their recommendations for the optimal time of the RxWBS ranging from 48 – 72 hours (Becker et al., 1996; Luster et al., 2008) to 2 – 10 days (Cooper et al., 2009). Also, there is a lot of discrepancy in the published literature regarding the optimal timing of RxWBS (Cholewinski et al., 2000; Chong et al., 2010; Durante et al., 2006; Hindie et al., 2003; Hung et al., 2009; Khan et al., 1994; Nemec et al., 1979). So far, several studies were done for evaluating efficacy or accuracy of RxWBS which was done at different timing after high-dose I-131 therapy. Khan et al. conducted scans at 2 days and 7 days post-therapy after 3.7–5.6 GBq of I-131 administration (Khan et al., 1994). They reported a higher sensitivity for detection of iodine-avid tissue on RxWBS 7 days post-therapy than earlier RxWBS. Hung et al. analyzed RxWBS at three different time points (first scan performed 3–4 days, second scan 5–6 days, and third scan 10–11 days after I-131 therapy) (Hung et al., 2009). They retrospectively analyzed 239 patients' scans. Twenty-eight percent of lymph node metastases, 17% of lung metastases, and 16% of bone metastases were missed on the late images on 10-11th day. On the other hand, only 5% of the remnants were missed. The ratio of early washout was different between remnants and metastatic lesions. Chong et al. conducted RxWBS on the third and seventh days after I-131 therapy in 60 cases from 52 patients with lung or bone metastases of thyroid cancer (Chong et al., 2010). They showed that 22% of lung metastases and 33% of bone metastases that were not shown on the third day scan were detected on the seventh day scan (Figure 4 and 5). Lee et al. conducted RxWBS on the third and tenth day after I-131 therapy in 81 patients (Lee et al., 2011). They reported that the I-131 avid lesions on the early scan were more easily detected by visual analysis and had higher uptake ratios than those on the delayed scan. The optimal timing for RxWBS is still needed to be clarified.

### **2.3 Medication and diet after administration of therapeutic dose of I-131**

Published guideline for I-131 therapy recommend that low-iodine diet, when possible, <50 μg/day, starting 1-2 weeks prior to radioiodine administration is recommended (Cooper et al., 2009; Luster et al., 2008). However, the duration of this low-iodine diet varies. Usually, regular diet can be started after the treatment. Information about low-iodine diet can be obtained at Thyroid Cancer Survivors Association website, http://www.thyca.org/rai.htm#diet.

Whole body imaging with SPECT/CT requires long scan time. Therefore, SPECT/CT is usually performed for specific site after whole body scan. The field of view (FOV) of SPECT/CT is usually determined by nuclear medicine physicians based on the planar image findings. So far, many companies have their models of SPECT/CT. This is the one of the usual protocol of SPECT/CT (Infinia Hawkeye 4) of our institution. First, emission SPECT images are acquired with counts from the 10% energy window at 364 KeV, with a matrix size of 128 x 128. A total image of 64 frames is acquired over 360 with an acquisition time of 30 s/frame, angular step of 6, and zooming factor of 1. After SPECT acquisition, a CT scan is acquired with a low-dose, helical CT scanner. The CT parameters are 140 KeV and 5 mAs, and no intravenous iodinated contrast is administered. The CT data are used for attenuation correction. The Images are reconstructed with a conventional iterative algorithm, ordered subset expectation maximization (OSEM). A workstation providing multiplanar reformatted

Radioiodine is excreted slowly in hypothyroid patients, especially if they have been on a low iodine diet (Dietlein et al., 2005). Therefore, decreasing background activity is important for visualizing small metastases or remnant thyroid tissue. However, current guidelines for I-131 therapy differ in their recommendations for the optimal time of the RxWBS ranging from 48 – 72 hours (Becker et al., 1996; Luster et al., 2008) to 2 – 10 days (Cooper et al., 2009). Also, there is a lot of discrepancy in the published literature regarding the optimal timing of RxWBS (Cholewinski et al., 2000; Chong et al., 2010; Durante et al., 2006; Hindie et al., 2003; Hung et al., 2009; Khan et al., 1994; Nemec et al., 1979). So far, several studies were done for evaluating efficacy or accuracy of RxWBS which was done at different timing after high-dose I-131 therapy. Khan et al. conducted scans at 2 days and 7 days post-therapy after 3.7–5.6 GBq of I-131 administration (Khan et al., 1994). They reported a higher sensitivity for detection of iodine-avid tissue on RxWBS 7 days post-therapy than earlier RxWBS. Hung et al. analyzed RxWBS at three different time points (first scan performed 3–4 days, second scan 5–6 days, and third scan 10–11 days after I-131 therapy) (Hung et al., 2009). They retrospectively analyzed 239 patients' scans. Twenty-eight percent of lymph node metastases, 17% of lung metastases, and 16% of bone metastases were missed on the late images on 10-11th day. On the other hand, only 5% of the remnants were missed. The ratio of early washout was different between remnants and metastatic lesions. Chong et al. conducted RxWBS on the third and seventh days after I-131 therapy in 60 cases from 52 patients with lung or bone metastases of thyroid cancer (Chong et al., 2010). They showed that 22% of lung metastases and 33% of bone metastases that were not shown on the third day scan were detected on the seventh day scan (Figure 4 and 5). Lee et al. conducted RxWBS on the third and tenth day after I-131 therapy in 81 patients (Lee et al., 2011). They reported that the I-131 avid lesions on the early scan were more easily detected by visual analysis and had higher uptake ratios than those on the delayed scan.

**2.1.2 SPECT/CT** 

images are used for image display and analysis.

The optimal timing for RxWBS is still needed to be clarified.

**2.3 Medication and diet after administration of therapeutic dose of I-131** 

Published guideline for I-131 therapy recommend that low-iodine diet, when possible, <50 μg/day, starting 1-2 weeks prior to radioiodine administration is recommended (Cooper et al., 2009; Luster et al., 2008). However, the duration of this low-iodine diet varies. Usually, regular diet can be started after the treatment. Information about low-iodine diet can be obtained at Thyroid Cancer Survivors Association website, http://www.thyca.org/rai.htm#diet.

**2.2 Imaging timing of RxWBS** 

Fig. 4. Diffuse pulmonary metastases. The metastatic uptake is not seen on I-123 DxWBS (A) and early RxWBS (on the third day after therapy) (B). It only appears on the RxWBS which was performed on the seventh day after the administration of 7.4 GBq (200 mCi ) I-131 (C).

Fig. 5. Multiple osseous metastases. The metastatic lesion in the upper thoracic vertebra (arrow) is only visible on the RxWBS obtained seventh day after administration of 7.4 GBq (200 mCi) I-131 (B). These lesion is not visible on RxWBS obtained third day after therapy (A) or Tc-99m HDP WBS (C).

Post-Therapeutic I-131 Whole Body Scan in Patients with Differentiated Thyroid Cancer 237

Fig. 7. Thymic uptake. A 12-year-old girl underwent therapy with 3.7 GBq (100 mCi) I-131. RxWBS were obtaind on the third day (A) and seventh day (B) after therapy. Hot uptakes are seen in the right lower neck and upper chest. I-131 SPECT/CT (C) and F-18 FDG PET/CT images (D) confirmed I-131 uptake in the upper chest to be physiologic uptake in

Diffuse hepatic uptake of I-131 is rarely found due to occult hepatic metastases but more commonly due to the hepatic de-ionization and conjugation of I-131 which was not incorporated into the thyroid hormone (Carlisle et al., 2003). Chung et al. investigated hepatic uptake on DxWBS or RxWBS. They analyzed scans of 399 patients. They reported that hepatic uptake is more often when higher dose of I-131 was administered. They also reported that the more uptakes appeared in the residual thyroid, the more it appeared in the liver. However, they found that 15 patients showed diffuse hepatic uptake without uptake by the remnant thyroid or metastatic lesion. They followed these patients and metastatic lesions were found in 7 of 15 patients. So, they insisted that diffuse liver uptake indicated

There are some reports I-131 false positive uptake in other pathologic condition unrelated to thyroid cancer: tracheostomy site, bronchiectasis, pulmonary inflammatory disease, pleural effusion, salivary gland tumor, some other carcinoma such as adenocarcinoma, squamous carcinoma, Barrett's esophagus, Meckel's diverticulum (Ain & Shih, 1994; Berquist et al., 1975; Caplan et al., 1987; Carlisle et al., 2003; Fernandez-Ulloa et al., 1976; Hoschl et al., 1988; Misaki et al., 1994; Mitchell et al., 2000; Muratet & Giraud, 1996), and so on. (Figure 9)

functioning thyroid remnant or metastasis (Chung et al., 1997) (Figure 8).

the thymus.

Thyroid hormone replacement may be resumed on the second or third day after therapy (Cooper et al., 2009; Luster et al., 2008).
