Comparison between ^99mTcO₄⁻ SPECT/CT and diagnostic ¹³¹I SPECT/CT for the detection of postoperative thyroid remnant in patients with differentiated thyroid cancer

Introduction

The incidence of thyroid cancer has been gradually increasing in recent years, currently representing the most common malignant neoplasm in the endocrine system. It is the seventh most common cancer in terms of incidence overall and fifth in females worldwide (1). However, its incidence in China has risen to the third in 2022 (2). Most thyroid cancers are well-differentiated thyroid cancer (DTC), with papillary thyroid cancer being the most prevalent subtype. Radioactive iodine (RAI) remnant ablation and/or adjuvant therapy is one of the standard treatments for DTC that consists of total thyroidectomy. Remnant thyroid tissue (RTT) is often present in 61.7–100% of patients at intermediate-to-high risk of recurrence who have undergone total thyroidectomy (3,4). Radioiodine remnant ablation (RRA) is recommended for intermediate- and high-risk DTC patients after total thyroidectomy, facilitating the detection of recurrent or metastatic lesions by thyroglobulin measurements or whole-body scan (WBS) (5). According to the 2025 American Thyroid Association (ATA) guidelines, a wide range of radioiodine doses, varying from low-dose radioiodine [1,110 MBq (30 mCi)] to high-dose radioiodine [3,700 MBq (100 mCi)], was recommended to RRA (5). The rate of successful remnant ablation with 30 mCi or 50 mCi has been reported to be not inferior to that with 100 mCi (6-8). However, some studies have also shown that an administered activity of 100 mCi was superior to 30 mCi or 50 mCi in achieving successful remnant ablation (9). In order to improve the success of the RRA, a ¹³¹I dose of 100 mCi was mostly used in clinical practice, and even higher radioiodine doses are sometimes administered. How to achieve effective RRA with a relatively optimal radioiodine activity remains a difficult problem in clinical practice. Hence, accurate imaging evaluation of RTT is a particularly important reference for precise RAI remnant ablation.

Ultrasound (US), ^99mTc pertechnetate scan, and diagnostic ¹³¹I scan have been frequently used to assess postoperative DTC patients. However, US is known to be a highly operator-dependent imaging modality and heavily relies on the US machine’s settings (10,11). False-positive results were reported in 57–67% of patients when US was used to monitor postoperative DTC patients, because postoperative scar tissue, necrosis, suture granulomas, etc., cannot be differentiated from RTT or metastatic lesions (12,13). Tc-99m is a widely used imaging agent in thyroid imaging. The sensitivity, specificity, and positive predictive value (PPV) of Tc-99m pertechnetate scan in evaluating RTT have been reported as being 61–81%, 70.5–100%, and 97.4–100%, respectively. However, the negative predictive value (NPV) was only 0–22% (4,14-17). The diagnostic ¹³¹I scan has been used to evaluate RTT, and the sensitivity ranged from 67% to 98.7% for detecting RTT in planar scintigraphy (18,19). However, due to the risk of a “stunning effect” of diagnostic ¹³¹I scan, it was not widely proposed for clinical use. Studies have shown that “stunning” may be mitigated or avoided by the use of either low-activity ¹³¹I (1–3 mCi) or ¹²³I. However, ¹²³I is difficult to prepare and costly; in addition, studies show that ¹²³I may also cause a “stunning effect” (20-24).

Currently, studies on preablation scintigraphy have mainly focused on comparing ^99mTc pertechnetate scan versus postablation ¹³¹I scan, or diagnostic ¹³¹I scan versus postablation ¹³¹I scan (17,25). In addition, these studies explored the role of planar images, and few investigations have focused on single photon emission computed tomography/computed tomography (SPECT/CT) (4,17,19). The utility of diagnostic ¹³¹I scans for guiding the therapeutic management of RAI continues to be debated. The addition of hybrid SPECT/CT has the potential to accurately identify specific anatomic areas of radioactive uptake (26,27). It enables more precise identification of radiotracer uptake in the cervical region, for example, differentiating radioactive uptake by central lymph nodes from that by residual thyroid tissue or cancerous lesions in the thyroid bed. Besides, there is a lack of literature analyzing RTT using diagnostic ¹³¹I whole body scan with SPECT/CT (Dx scan) in a large sample.

The 2025 ATA guidelines outline an approach to clinical decision-making based on the individual journey of thyroid cancer patients and clinicians, which is termed DATA: Diagnosis, risk/benefit Assessment, Treatment decisions, and response Assessment (5). Dx scan may be an important reference for the DATA framework, but its value has not yet been fully explored. Hence, this study aimed to identify anatomic sites of RTT, compare the performance of Dx scan and ^99mTcO₄⁻ SPECT/CT (Tc-99m scan) in analyzing RTT, indicate possible limitations of Tc-99m scan for assessment of RTT, and obtain accurate preablation imaging for the assessment of RTT, allowing for individualized dosing of RAI therapy. We present this article in accordance with the STARD reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1-2776/rc).

Methods

Patients

This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This retrospective study was approved by the Institutional Review Board of the Sixth Affiliated Hospital of Sun Yat-sen University (No. 2022ZSLYEC-438). The requirement for informed consent was waived due to the retrospective nature of the study. The medical records of 505 patients who received ¹³¹I treatment from January 2020 to December 2021 at the Sixth Affiliated Hospital of Sun Yat-sen University were retrospectively reviewed. Demographics, clinical characteristics, laboratory data, tumor-node-metastasis (TNM) stage, and recurrence risk stratification were collected. Blood samples were obtained from all patients, and thyroid-stimulating hormone (TSH), stimulated thyroglobulin (sTg), and thyroglobulin antibody (TgAb) were measured before ¹³¹I administration through Abbott Laboratories (Chicago, IL, USA). According to Dekker et al., TgAb <10 IU/mL was considered negative and TgAb ≥10 IU/mL was considered positive in our study (28). Patient preparation included thyroid hormone withdrawal and a low iodine diet for 3 weeks.

Inclusion and exclusion criteria

In this study, patients were enrolled if they met the following criteria: (I) underwent total thyroidectomy, and postoperative histopathological examination confirmed the diagnosis of papillary thyroid carcinoma in each case. Histopathological evaluation included tumor subtype, extrathyroidal extension, lymph node metastasis, and resection margin status, based on the World Health Organization (WHO) classification of thyroid tumors; (II) had precise TNM staging in accordance with the eighth edition of the Thyroid Cancer Staging Criteria of the American Joint Committee on Cancer; (III) performed both Tc-99m scan and Dx scan before RAI and postablation ¹³¹I SPECT/CT (Rx scan) after therapy; and (IV) received RAI for the first time and showed a serum TSH level more than 30 µIU/mL before ¹³¹I treatment. Patients were excluded from this study if they met any of the following criteria: (I) underwent near-total or subtotal thyroidectomy; (II) lacked information about the primary tumor; (III) were pregnant or of childbearing age; and (IV) had recurrence and/or metastases after total thyroidectomy (confirmed by surgical records, histology, US, CT, SPECT/CT, or PET/CT).

Successful remnant ablation criteria

The individual RRA dose for each patient is determined based on recurrence risk stratification, sTg levels, TgAb status, and imaging evaluation. Successful remnant ablation can be defined by an undetectable sTg level in the absence of interfering TgAb, along with no radioiodine uptake on a Dx scan. An alternative definition in cases in which TgAb is present is the absence of visible RAI uptake on a subsequent Dx scan.

Imaging protocols

All SPECT/CT were performed on a hybrid variable-angle dual-head γ-camera, Symbia Intevo 6 system (Siemens Healthcare, Erlangen, Germany).

^99mTc-pertechnetate scan

A ^99mTc-pertechnetate scan was performed 30 minutes after intravenous injection of 6 mCi (222 MBq) of ^99mTc-pertechnetate with patients lying supine on the imaging bed. SPECT/CT detector equipped with a low-energy and high-resolution parallel-hole collimator (matrix 128×128, zoom 1.23, using a 15% window at 140 keV photopeak) in 32 projections (17 seconds/stop) with a noncircular orbit of approximately 180 degrees was implemented, followed by low-dose CT examination. The CT scanning parameters were as follows: 40 mAs, 120 keV, 2.5 mm collimation, and a 45-cm field of view (FOV). The tomographic images were reconstructed with the iterative method (ordered-subsets expectation maximization) and a CT-based attenuation correction algorithm was applied.

Diagnostic ¹³¹I scan with SPECT/CT and postablation ¹³¹I scan with SPECT/CT

At 24 hours after patients taking 2 mCi (74 MBq) ¹³¹I orally, a planar WBS was obtained in anterior and posterior projections. Static images were acquired for 10 minutes using detectors fitted with parallel-hole and high-energy collimators (256×1,024 matrix, zoom 1, matching a 15% window at 364 keV peak). The scan speed was set as 21 cm/minute. All patients underwent conventional SPECT/CT imaging with an axial FOV centered in the cervical region/thyroid bed. SPECTs were acquired (128×128 matrix, zoom 1, 15% energy windows at 364 keV). Then, CT was taken using the Tc-99m scan protocol described. At 4–6 hours after completing the Dx scan, patients underwent RAI with 1,850–3,700 MBq ¹³¹I. On day 2–3 after administering an orally therapeutic ¹³¹I dose, an Rx scan was performed using the same protocol and equipment as the Dx scan.

Anatomic localization of ¹³¹I uptake sites

The three kinds of images were independently analyzed by two experienced nuclear physicians. All disagreements were resolved by reaching consensus. In this study, Rx scan served as the “gold standard” for identifying RTT. The thyroid bed area was divided into superior and inferior compartments based on the proximity of the inferior border of the thyroid cartilage. The superior compartment was further divided into three anatomical regions (Figure 1): (I) superior anterior region (SAR): around anterior and midline to the larynx, components of thyroglossal duct and the pyramidal lobe; (II) and (III) superior left lateral region (SLLR)/superior right lateral region (SRLR): lateral to the thyroid cartilage (both sides). Additionally, the inferior compartment was divided into five parts: (I) inferior anterior region (IAR): anterior to the trachea, and associated with the thyroid isthmus; (II) and (III) inferior left anterolateral region (ILAR)/inferior right anterolateral region (IRAR): anterolateral to the trachea (both sides), where Berry’s ligament anchors the thyroid gland to the trachea; (IV) and (V) inferior left posterolateral region (ILPR)/inferior right posterolateral region (IRPR): posterolateral to the trachea (both sides), in the tracheo-esophageal groove and posterolateral tracheal region on either side. Any focal ¹³¹I uptake above the background in these 8 regions was considered to be true positive, indicating the presence of RTT, whereas no uptake observed in the thyroid bed was considered negative. Foci of ¹³¹I uptake clearly located outside the 8 regions or those with corresponding structural evidence of metastases evaluated by CT were excluded from the analysis.

Figure 1 Distribution of remnant thyroid tissue in the thyroid bed.

Statistical analysis

All statistical analyses were performed using the software SPSS 23.0 (IBM Corp., Armonk, NY, USA). Quantitative data were presented as mean ± standard deviation (SD). Differences in continuous variables across groups were assessed by t-test or analysis of variance (ANOVA) if data followed a normal distribution; otherwise, either the Mann-Whitney U test or Kruskal-Wallis H test was applied. Differences in categorical variables between groups were evaluated using the Pearson’s chi-squared test. Sensitivity, specificity, accuracy, PPV, and NPV of both Tc-99m scan and Dx scan for detecting RTT were calculated. Spearman’s rank correlation coefficient was used to show the association of the number of thyroid remnants with sTg levels and sTg/TSH ratio. To balance baseline characteristics between the 50 mCi and 100 mCi groups in the SAR-positive subgroup, propensity score matching (PSM) was performed using a 1:1 nearest-neighbor algorithm with a caliper of 0.2 SDs of the logit propensity score. Matching covariates included sex, age, T stage, N stage, TgAb status, and sTg. After matching, multivariable logistic regression adjusting for the same covariates was used to estimate the independent effect of RAI dose on ablation success. A P value less than 0.05, was defined to indicate statistical significance.

Results

A total of 505 patients were evaluated retrospectively, and 68.3% were female, with a mean age of 39 years (8–74 years). The baseline information of participants is shown in Table 1.

Per-patient analysis

Of the 505 patients, 12 (2.4%) had negative Rx scans, Dx scans, and Tc-99m scans. Of the remaining 493 patients who had positive Rx scans, 326 (66.1%) had positive Tc-99m scans, and 470 (95.3%) had positive Dx scans. Neither Dx scans nor Tc-99m scans showed false-positive results. In the per-patient analysis, Tc-99m scans had a sensitivity of 66.1% and an NPV of 6.7%, whereas Dx scans demonstrated a significantly higher sensitivity of 95.3% and an NPV of 34.3%; both modalities achieved 100% specificity and PPV (Table 2).

Of the 167 patients with false-negative Tc-99m scans, 144 (86.2%) were positive on Dx scans (Figure 2). No patient was found positive on Tc-99m scans but negative on Dx scans.

Figure 2 Tc-99m scan compared with the Dx scan and Rx scan. A 32-year-old male after total thyroidectomy with an sTg was 0.05 ng/mL. No RTT was seen on the Tc-99m scan (A-D), whereas RTTs in the IRPR, ILPR, SRLR, and SAR with positive uptake were seen on the Dx scan (E-H) and Rx scan (I-L). Dx scan, diagnostic ¹³¹I scan with SPECT/CT; ILPR, inferior left posterolateral region; IRPR, inferior right posterolateral region; RTT, remnant thyroid tissue; Rx scan, postablation ¹³¹I scan with SPECT/CT; SAR, superior anterior region; SRLR, superior right lateral region; sTg, stimulated thyroglobulin; Tc-99m scan, ^99mTcO₄⁻ SPECT/CT.

Per-site analysis

A total of 1,057 positive foci were detected on Rx scans, including 432 located in the superior compartment and 625 in the inferior compartment. In the superior compartment, 66.2% (286/432) of RTT sites were situated in the SAR, whereas in the inferior compartment, RTTs were mainly located in the ILPR/IRPR (66.2%, 414/625), followed by the ILAR/IRAR (30.1%, 188/625). Detailed distribution of the number of RTT in all the 8 regions by T and N stage is shown in Table S1.

Of the overall 1,057 positive foci, 500 and 916 were shown on Tc-99m scans and Dx scans, respectively. In the per-site analysis, the overall sensitivity, specificity, PPV, and NPV of Tc-99m scans detecting RTT were 47.3%, 100%, 100%, and 84.3%, whereas the corresponding values for Dx scans were 86.7%, 100%, 100%, and 95.5%. Dx scans demonstrated significantly superior sensitivity to Tc-99m scans for detecting RTT across all eight regions (P<0.001) (Table 3).

Interestingly, a marked regional variation in sensitivity was observed, and the SAR yielded the highest sensitivity for both Tc-99m and Dx scans. The sensitivity of Tc-99m scans detecting RTT in SAR was 74.8%, significantly higher than that in the other 7 regions (all P<0.001). For Dx scans, the sensitivity for RTT in SAR was also higher than that in the other regions except the ILPR (all P<0.05; Table 3).

Associations of sTg, TgAb, TSH, and sTg/TSH with different modalities

As shown in Table 4, sTg and sTg/TSH levels in patients with positive Tc-99m scan were significantly higher than those in Tc-99m scan-negative patients. The same trend was observed for Dx scans (all P<0.05). In contrast, TgAb levels were significantly lower than in scan-negative patients (both P<0.05). There were no significant differences in age at diagnosis, sex, T stage, N stage, and recurrence risk between positive scan and negative scan (Table S2). Considering the interference of TgAb with sTg, patients were further divided into two groups: TgAb ≥10 IU/mL and TgAb <10 IU/mL. Regardless of TgAb status, sTg and sTg/TSH in the Tc-99m scan positive group were significantly higher than those in the corresponding Tc-99m scan negative group, and this association was also observed for Dx scans (all P<0.05).

The 470 patients with positive Dx scans were further divided into two subgroups: Dx scan (+)/Tc-99m scan (−) and Dx scan (+)/Tc-99m scan (+), as shown in Table S3. Patients in the Dx scan (+)/Tc-99m scan (−) subgroup had significantly lower sTg and sTg/TSH levels than those in the Dx scan (+)/Tc-99m scan (+) subgroup (P<0.001), whereas no significant difference in TgAb levels was observed between the two subgroups (P>0.05).

Furthermore, the median sTg and sTg/TSH levels of patients with positive SAR uptake on Rx scans were significantly higher than those with negative SAR uptake (1.96 vs. 0.61 ng/mL, P<0.001; 0.020 vs. 0.008, P<0.001), but there was no difference in TgAb (3.36 vs. 2.83 IU/mL, P=0.313).

Analysis of RTT counts on Rx scans showed that 88.7% of patients had 1–3 RTT foci (Table S4). The number of RTT showed a weak positive correlation with serum sTg (rs=0.155, P<0.001) and sTg/TSH ratio (rs=0.160, P<0.001).

Results of RRA for RTT

Subsequent to RRA, follow-up Dx scans at a median interval of 6 months were performed in 427 (90.9%) of the 470 patients with initially positive Dx scans. The RAI doses were 50 mCi for 340 patients and 100 mCi for the remaining 87. The success rate of RRA was significantly higher in the 100 mCi group than in the 50 mCi group (97.7% vs. 90.0%, P=0.021). Among the 427 patients with positive Dx scans, 58.3% (249/427) had positive uptake in the SAR. Patients with SAR uptake who received the 100 mCi dose had a significantly higher ablation success rate (96.8%, 61/63) than those who received the 50 mCi dose (88.2%, 164/186) (P=0.044). Due to the substantial imbalance in sample size between the two dose groups, PSM was performed. After matching, the ablation success rate remained higher in the 100 mCi group than in the 50 mCi group [98.3% (58/59) vs. 86.4% (51/59)], and multivariable logistic regression confirmed that the 100 mCi dose was associated with significantly higher odds of ablation success [odds ratio (OR) =9.098, 95% confidence interval (CI): 1.100–75.24, P=0.037]. However, for the remaining SAR-negative uptake patients, the ablation success rate was not significantly higher with the 100 mCi dose than with the 50 mCi dose [100% (24/24) vs. 92.2% (142/154), P=0.157].

Discussion

Based on the 2025 ATA guidelines, surgery is the main treatment for DTC, but RTT is usually present even after total thyroidectomy and is detected in the thyroid bed in 93.9–100% of patients (5,17,19). Our study suggested that the incidence rate of RTT on Rx scans was as high as 97.6%. During total thyroidectomy, surgeons must balance thorough thyroid tissue removal against the risk of consequences such as recurrent laryngeal nerve injury and hypoparathyroidism. Hence, some RTT around the upper parathyroid gland and the entrance of the recurrent laryngeal nerve are maintained to safeguard these structures (29). We delineated 8 RTT predilection sites, similar to previous studies (15,26). Due to anatomical ambiguity on SPECT/CT images, the superior pole was not subdivided into anterior and posterior compartments. The reported anatomical distribution of RTT varies across studies. Holsinger et al. reported that RTT is mostly located in the thyroid bed paratracheal echelon (in 84% of patients), equivalent to the inferior posterolateral region (30). However, Bulzacka et al. found that RTT located in the superior anterior region, Berry’s ligaments area, and posterolateral to the trachea accounted for 33%, 21%, and 26% of all RTT, respectively (15). Zeuren et al. found that RTT on SPECT/CT was most commonly located in the regions of Berry’s ligaments in 87% of patients, followed by the superior thyroid poles (79%), paratracheal-lobar regions (67%), and isthmus (53.9%) (26). In our research, 1–3 RTTs could be found in most patients who underwent total thyroidectomy, and the majority of thyroid remnants were situated in the ILPR/IRPR, followed by SAR regardless of T stage or N stage. The assumption may be that the tracheo-esophageal groove and lateral thyroid region are anatomically situated in a deep and inaccessible location, leading to RTT. The incidence of RTT in the IAR was low in both cohorts: 4.6% (23/505) in the present study and 9.0% (9/100) in a previous report (15). We assume that this low prevalence is due to the superficial anatomical location of the site that facilitates complete surgical resection.

Based on the DATA framework of the 2025 ATA guidelines, dynamic risk assessment is a key reference for decision-making in RAI therapy (5). However, relying solely on sTg levels is insufficient for precisely determining individualized treatment doses. Nuclear medical imaging is the most important evaluation method for RAI treatment. There are still no definitive recommendations on whether to perform a Tc-99m pertechnetate scan or a preablation ¹³¹I scan before RAI therapy. All patients underwent both Tc-99m scans and Dx scans before ¹³¹I administration, and we found that the Dx scan was more sensitive than the Tc-99m scan for RTT evaluation, both in per-patient and per-site analyses. In the study, 86.2% of patients with negative Tc-99m scans had positive Dx scans, and 42.9% of patients with positive Tc-99m scans had more RTT detected on Dx scans. Due to no false-positive patients, the specificity and PPV of Dx scans and Tc-99m scans were as high as nearly 100%. Previous literature reported that the NPV of Tc-99m scans was as low as 14.2% and 26% of patients had false negative Tc-99m scans, but specificity of Tc-99m scans in their study was lower than that in ours (70.4% vs. 100%) (17), which may be related to the fact that their study was based on planar scintigraphy. Hence, negativity in Tc-99m scan may not indicate the absence of RTT. Consequently, some researchers suggested further Dx scans for those with equivocal or negative Tc-99m scans to confirm the existence of positive uptake (16). It can be presumed that Tc-99m imaging underestimates the burden of RTT or tumor relative to Dx scans, affecting the accuracy of the assessment before ¹³¹I treatment. For ¹³¹I therapy, Dx scans are essential not only for positive lesions detection but also for clinical management. Previous studies have shown that Dx scans can provide information changes staging in 4–25% of patients, modify risk stratification in 15% of patients and alter clinical management in 29.4% to 53% of patients (25,31,32).

Both Tc-99m scan and Dx scan showed higher sensitivity for detecting RTT in the pyramidal lobe/thyroglossal duct region than in other areas. This may be attributed to the increased sodium–iodide symporter (NIS) gene expression in ectopic thyroid tissue under TSH stimulation, thereby improving the visualization of thyroglossal duct remnants (33-35). Previous studies have shown that ^99mTc-pertechnetate planar scintigraphy overlooked uptake in the sites in euthyroid condition, but that the uptake became visible under TSH stimulation (36,37). In our study, patients with positive SAR uptake exhibited noticeably higher sTg levels. We speculate that functional thyroid tissue in SAR may contribute to elevated levels of circulating thyroglobulin. This observation is consistent with a previous report where thyroglossal duct uptake was linked to higher sTg (12.63 vs. 6.85 ng/mL) (35). It is important to note, however, that the absolute sTg values in that study were higher than in ours, a difference likely attributable to their inclusion of patients with near-total thyroidectomy.

In the study, the association between different imaging groups and sTg and TgAb levels was further analyzed. Given that sTg levels are TSH-dependent, we also calculated the sTg/TSH ratio, which was reported to have a strong association with the therapeutic effect of the first ¹³¹I treatment, similar to sTg (38,39). sTg levels and sTg/TSH ratio are essential parameters for measuring the volume of RTT and predicting metastases in patients with DTC (14,15,17,20,40-42). We found that positive findings on both Tc-99m and Dx scans were consistently associated with significantly elevated sTg and sTg/TSH ratios, regardless of TgAb status—a pattern previously reported by Lan et al., who observed lower sTg levels in patients with negative Tc-99m scans (2.94 vs. 4.58 ng/mL) (41). Furthermore, among patients positive on Dx scans, those with negative Tc-99m scans (n=144) had significantly lower sTg and sTg/TSH ratios than those with positive Tc-99m scans. This suggests that although a negative Tc-99m scan does not exclude RTT, it may indicate a smaller burden. Conversely, a positive Tc-99m scan likely reflects a larger RTT volume.

Despite concerns that Dx scans may induce a “stunning effect” and potentially compromise subsequent ¹³¹I therapy, the existence and clinical impact of this phenomenon remain contentious (23,43-45). Indeed, several studies argue that the line between therapeutic ablation and imaging-induced stunning is often blurred (46). Moreover, several retrospective studies with large samples indicated that Dx scans with low-dose radioiodine (1–5 mCi) has no effect on the success rate when ¹³¹I therapy is administered within 48–72 hours of the Dx scan (18,47-49). This study found no evidence that Dx scans caused a “stunning effect”, as Rx scans identified all Dx-detected RTT and even revealed additional foci, culminating in a high ablation success rate of over 90%. We attribute these outcomes to the low 2 mCi activity of Dx scans and the short interval (within 6 hours) to subsequent radioiodine therapy. Furthermore, although the 100 mCi ablation dose was more effective than 50 mCi for residual thyroid tissue, this benefit was confined to patients with positive SAR uptake, for whom the higher dose is therefore recommended. In SAR-negative patients, the 50 mCi dose was equally effective. Thus, given the lack of evidence for dose escalation to 100 mCi, the 50 mCi regimen may be preferred to avoid unnecessary radiation exposure. However, because dose assignment was not randomized, unmeasured confounding factors (e.g., RTT volume or clinician preference) may have influenced the observed outcomes. Moreover, the recommendation of 100 mCi for SAR-positive patients remains preliminary given the limited sample size. Prospective randomized studies and external validation in larger, multicenter cohorts are required before clinical implementation.

Several limitations also exist in our study. Firstly, this study is limited by its retrospective, single-center design, which may introduce selection bias and limit generalizability. Future multicenter prospective studies are warranted to validate our findings. Secondly, the ¹³¹I/^99mTc-pertechnetate uptake was not quantitatively assessed. Future studies incorporating semi-quantitative or quantitative parameters [e.g., %ID/g or standardized uptake value (SUV)] are needed to better guide personalized radioiodine therapy. Thirdly, the utility of Dx scans for detecting recurrence or distant metastases was not evaluated in this study, representing an important direction for future research. Nonetheless, our findings confirm that Dx scans can detect more RTTs than Tc-99m scans, even in patients with lower sTg levels and smaller RTT volumes. Long-term follow-up for recurrence or metastasis is ongoing and will be essential to confirm whether the higher sensitivity of Dx scans translates into meaningful clinical benefit.

Conclusions

In this study, the 74 MBq ¹³¹I Dx scan was well correlated with Rx scan and was more reliable for detecting RTT in postoperative DTC patients than Tc-99m scan. The association between positive SAR uptake and higher sTg levels underscores the importance of accurate RTT assessment in ensuring successful RRA. A 74 MBq ¹³¹I Dx scan enables the precise evaluation of RTT, thereby facilitating accurate RRA.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STARD reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1-2776/rc

Data Sharing Statement: Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1-2776/dss

Funding: This research was supported in part by the Natural Science Foundation of Guangdong Province, China (No. 2023A1515011300), and the State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia & The First People’s Hospital of Kashi Fund (No. SKL-HIDCA-2020-KS2).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1-2776/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This retrospective study was approved by the Institutional Review Board of the Sixth Affiliated Hospital of Sun Yat-sen University (No. 2022ZSLYEC-438). The requirement for informed consent was waived due to the retrospective nature of the study.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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