THYROID Volume 25, Number 8, 2015 ª Mary Ann Liebert, Inc. DOI: 10.1089/thy.2014.0521

The Use of 123I in Diagnostic Radioactive Iodine Scans in Children with Differentiated Thyroid Carcinoma Melissa J. Schoelwer,1 Donald Zimmerman,2 Richard M. Shore,3 and Jami L. Josefson 2

Background: Adult studies have shown that iodine-123 (123I) is as effective as 131I in detecting metastatic disease in patients with differentiated thyroid carcinoma. However, the type and administered activity of radioiodine used for diagnostic imaging of metastatic thyroid cancer has not been well studied in children. Here we describe our institution’s experience with using 123I in diagnostic radioiodine scans in children with differentiated thyroid carcinoma. Methods: Every patient with differentiated thyroid carcinoma who completed diagnostic scanning followed by radioiodine therapy at our institution over the past 8 years was included in this retrospective chart review. Patient age, sex, presentation of thyroid disease, past medical history, thyrotropin, thyroglobulin, and antithyroglobulin antibodies were recorded. A single nuclear medicine radiologist evaluated all scans. Results: Thirty-three subjects completed 37 pairs of scans at a mean age of 13.4 years (range 6–17 years). The majority of subjects were female (81%) and had papillary thyroid cancer (91%). For diagnostic scanning, 5 received 2 mCi of 131I, 21 received 2 mCi of 123I, and 11 received 3 mCi of 123I. There was no statistically significant difference in rate of discordant scan pairs when comparing 131I and 123I (20% and 23% respectively, p = 0.9). The detection of metastatic pulmonary disease on diagnostic scanning was not improved by increasing the dose of 123I from 2 mCi to 3 mCi (10% rate of missed lung detection with 2 mCi 123I vs. 20% with 3 mCi 123I). Conclusions: 123I is effective for use in diagnostic radioactive iodine scans in children with differentiated thyroid cancer. The primary advantages of using 123I include decreased radiation exposure and avoidance of stunning. However, in children there is a possibility of missed detection of metastatic pulmonary disease.

Introduction

C

hildren with differentiated thyroid carcinoma (DTC) have a greater risk of metastatic disease when compared with adults, particularly to the lymph nodes in papillary thyroid carcinoma and lungs in both papillary and follicular thyroid carcinoma (1,2). Despite the high frequency of metastatic disease at diagnosis of DTC, the long-term prognosis in children is excellent (2–5). Following thyroidectomy, testing for residual disease and metastases is accomplished through a combination of diagnostic whole-body scanning with low-dose radioactive iodine (RAI), neck ultrasounds, and serial thyroglobulin (Tg) measurements. Thyroid tissue is iodine-avid; thus, diagnostic scans are commonly performed with one of two different radioactive iodide isotopes, 131I or 123I. Iodine-131 emits both b- and c-radiation (6), whereas 123I emits pure c-radiation. The cradiation emitted by both radioisotopes is used for imaging as it travels long distances through tissue. The b-radiation

emitted by 131I causes thyroid cell destruction, which allows for use in therapeutic tumor eradication in which large doses of RAI are given to completely destroy all thyroid tissue, including malignant cells. 123I has a shorter physical half-life than does 131I (13.3 hours vs. 8 days). This is another feature that contributes to it causing substantially less damage to thyroid tissue than does 131I, along with causing a lower totalbody radiation burden (7,8). 123I is, however, more expensive and less readily available than is 131I. The main disadvantage of 131I in diagnostic scanning for local and distant metastatic disease is thyroid tissue ‘‘stunning.’’ This phenomenon occurs when the small diagnostic dose of 131I causes radiation injury to thyroid tissue and interferes with iodine uptake with subsequent administration of the larger therapeutic 131I dose (9). There is evidence that administration of even low doses of diagnostic 131I ‘‘stuns’’ thyroid cancer cells, making them less avid for the higher doses of 131I used for treatment purposes a short time later (6,10–13).

1 Division of Endocrinology, Riley Hospital for Children, Department of Pediatrics, Indiana University School of Medicine Indianapolis, Indiana. Divisions of 2Endocrinology and 3Radiology and Nuclear Medicine, Ann and Robert H. Lurie Children’s Hospital of Chicago, Department of Pediatrics and Radiology, Northwestern University Feinberg School of Medicine Chicago, Illinois.

935

936

To avoid the risk of stunning, many thyroid cancer treatment centers have shifted to using 123I in diagnostic scanning for metastatic thyroid disease. Adult studies have shown that diagnostic scans using 123I are as effective as those using 131I through comparison with posttreatment 131I scans or Tg measurements (6,7,14). Posttreatment scanning following high-dose 131I treatment can be considered a gold standard imaging technique since it has been found to be more sensitive than pretreatment low-dose 131I scans and since it can detect foci of uptake not previously seen on low-dose pretreatment scans in 10–30% of cases (6,15,16). The sensitivity of diagnostic scans using 131I has been found to be related to the dose administered (15). Although the utility of 123I in diagnostic scanning for DTC has been shown in adults, this has not yet been documented in children with DTC. Furthermore, the optimal dose of 123I for use in diagnostic scanning in children with DTC has not been established. The main objective of this study was to describe our institution’s experience using 123I in diagnostic wholebody scanning in children with DTC through comparison with 131I posttreatment scans. We also sought to determine if an increased dose of 123I (from 2 mCi to 3 mCi) provides better detection of metastatic pulmonary disease in children with DTC. We hypothesized that 123I would be as effective as 131 I in diagnostic scanning as previously seen in adults and that increasing the dose of 123I would result in better concordance rates between pre- and posttreatment scans. Materials and Methods

All consecutive patients with DTC and evidence of metastatic thyroid tumor treated at Ann and Robert H. Lurie Children’s Hospital of Chicago who completed diagnostic scanning followed by RAI therapy at our institution from 2005 to 2013 were included in this retrospective review. This study was approved by the Lurie Children’s Institutional Review Board. All patients had previously undergone total thyroidectomy and lymph node dissection, with the exception of one patient with follicular thyroid carcinoma who did not undergo lymph node dissection. Serum levels of thyrotropin (TSH), Tg, and anti-Tg antibodies obtained around the time of RAI dosing were recorded. Tg was measured using Siemens Immulite 2000, a chemiluminescent assay with a lowest detectable limit of 0.2 ng/mL. Scans

A total of 37 pairs of pretreatment and posttreatment scans were evaluated by one nuclear medicine radiologist to determine concordance. Scans were considered concordant when similar areas of uptake were seen on both the diagnostic and treatment scan and discordant when there were different areas of uptake seen on the scan pairs. Most of the diagnostic scans in this case series were the initial staging scans that were done approximately 6 weeks after thyroidectomy. The interval between diagnostic and treatment scans was typically 1–2 months. Patients were either withdrawn from thyroid hormone replacement 2 weeks prior to scanning or were given recombinant TSH (Thyrogen) to increase TSH level and improve scan sensitivity. Patients who received 131I for diagnostic scanning were given 2 mCi in accordance with the protocol in place prior to our institution’s switching to 123I for diagnostic scanning.

SCHOELWER ET AL.

Patients who received 123I for diagnostic scanning were given either 2 mCi or 3 mCi. Diagnostic scanning was performed 24 hours after oral ingestion of radioiodine. The 131I treatment dose was based on diagnostic scan uptake, the age and body surface area of the child, and the serum Tg level. Posttreatment scanning was performed 7 days after the administration of 131I. Statistical analysis

Concordance rates were calculated using the following equation: number of concordant scans/total number of scans compared · 100. Concordance rates among the two types of radioisotopes were compared using a two-tailed chi-square test. Results

A total of 33 patients completed 37 pairs of scans. For diagnostic scanning, 5 patients received 2 mCi of 131I, 21 patients received 2 mCi of 123I, and 11 patients received 3 mCi of 123I. Patient characteristics are outlined in Table 1. The mean age was 13.4 years with a range of 6 to 17 years. The majority of patients were female (81%) and had either papillary thyroid cancer (n = 30; 91%) or follicular thyroid carcinoma (n = 3; 9%). One patient with follicular thyroid carcinoma had Hu¨rthle cell changes (patient ID 13). Two patients developed secondary thyroid cancers; one 5 years after treatment for neuroblastoma (ID 2), the second (ID 17) 14 years following treatment for pre-B-cell acute lymphocytic leukemia (ALL). The patient with neuroblastoma did not receive any irradiation; however, the patient with ALL had received total body irradiation. Scan results are displayed in Table 2 along with TNM stage (17), TSH, Tg, and anti-Tg antibody levels when available. There was no statistically significant difference in rate of discordant scan pairs between 131 I and 123I (20% for 131I and 23% for 123I; p = 0.9), and prediagnostic scan TSH levels were appropriately elevated in all discordant scan pairs (range 36.24–270.3 lU/mL). Diagnostic scans were concordant with treatment scans in four of the five scan pairs when 2 mCi of 131I was used, and the diagnostic scans did not miss detection of lung disease. However, one patient (ID 4-A) was determined to have possible stunning with decreased uptake seen on the treatment scan compared with the diagnostic scan (Fig. 1). Diagnostic scans were concordant with treatment scans in 18 of the 21 scan pairs when 2 mCi of 123I was used. Figure 2 shows representative concordant scan images of patient ID 6. Two patients (ID 10, ID 14) were noted to have lung uptake

Table 1. Patient Characteristics Diagnostic Number scan of scans Total

37

2 mCi

131

I

5

2 mCi

123

I

21

3 mCi

123

I

11

Sex 30 7 4 1 16 5 10 1

female male female male female male female male

Mean age (range)

Type of cancer (%)

13.4 years 30 PTC (91) (6–17 years) 3 FTC (9) 9.4 years 5 PTC (100) (6–14 years) 0 FTC (0) 13.9 years 19 PTC (90) (6–17 years) 2 FTC (10) 14.1 years 10 PTC (91) (11–17 years) 1 FTC (9)

FTC, follicular thyroid carcinoma; PTC, papillary thyroid carcinoma.

123

I IN CHILDREN WITH DIFFERENTIATED THYROID CARCINOMA

937

Table 2. Diagnostic Scans 131

ID 2 mCi 1 2c 3 4-A 5 2 mCi 4-B 6 7 8 9 10

131

I Tx dose (mCi)

171 28.6 95.5 171 156 100 55.4 72.5 72.5

12 13 14

85 104 175

15 16 17d 18

70 27 48.6 190

19

95.6

20 21 22 23 24

28 28.3 100 27 93.5 123

Absb

TNM stage

Neck focus Neck foci Neck foci and lung uptake Neck focus on Dx scan, no uptake on post-Tx scan Neck foci and lung uptake

65 70 186 165

801 9.8 185 9.6

– – 355 –

T3N1M0 T3N1M0 T2N1M1 T2N0M0

327

241

641

T2N1M0

1 Neck focus Multiple neck foci and lung uptake Neck foci Neck foci Neck foci Neck foci on both scans, + lung uptake on Tx scan 1 Neck focus No uptake on Dx scan, + mediastinum uptake on Tx scan (likely thymus) Neck foci Neck foci Neck foci on both scans, + faint lung uptake on Tx scan Neck foci 1 Neck focus Neck foci Neck foci, lung uptake and proximal radius focus on both scans No uptake on Dx scan, 1 neck focus on Tx scan Neck foci Neck foci Neck foci 1 Neck focus Neck foci on both scans, + mediastinum uptake on Tx scan (likely thymus)

61 146 72 N/A 113 152

2.4 920 N/A N/A < 0.2 51

– – – – 31 –

T2N0M0 T3N1M1 T1N1M0 T2N1M0 T2N1M0 T3N1M1

61 187

15.4 20.4

– –

T3N0M0 T3N0M0

135 146 215

< 0.2 2.5 5.8

71 62 127

T3N1M0 T3N0M0 T3N1M1

343 150 59 74

23.7 0.3 4.8 133

– – – –

T3N1M1 T1N1M0 T1N1M0 T3N0M1

61

3.5



T3N1M0

186 21 168 189 112

N/A 1.1 < 0.2 < 0.2 279

– – – – –

T1N1M0 T3N0M0 T1N1M0 T1N1M0 T1N1M0

No uptake on Dx scan, 2 discrete mediastinum foci on Tx scan 3 neck foci Neck, mediastinum and axillary uptake on both scans, + lung uptake on Tx scan Neck foci on both scans, + lung uptake on Tx scan Neck foci Neck foci Neck foci Neck foci Neck and mediastinum uptake on both scans, + lung uptake on Tx scan (Chest CT negative for disease = false positive RAI scans) Neck foci on both scans; + mediastinum focus and thymus on Tx scan Neck foci

36

33.6



T3N1M0

147 270

0.3 1883

283 76

T2N1M0 T3N1M1

83

286

80

T3N1M1

89 273 55 145 91

1673 < 0.5 < 0.2 9.5 < 0.2

– 99 – – –

T3N1M0 T1N1M0 T1N1M0 T3N0M0 T2N0MX

159

0.5

910

T3N1M0

134

0.3



T3N1M0

1 2 2 1

I 96.6

26 27-A

120 130

27-B

120

28 29-A 29-B 30 31

90 55 71.3 29.9 150

32

103

33

80

a

Tg ng/mL

I

11-A 11-B

3 mCi 25e

TSH lU/ml

I 96.6 41.8 85.6 28.6

123

Scan comparison Dx vs. Txa

Scan descriptions listed in bold are considered discordant. Thyroglobulin antibodies: reference range,

The Use of 123I in Diagnostic Radioactive Iodine Scans in Children with Differentiated Thyroid Carcinoma.

Adult studies have shown that iodine-123 ((123)I) is as effective as (131)I in detecting metastatic disease in patients with differentiated thyroid ca...
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