Correlation analysis between the quantitative parameters of iodine-131 single-photon emission computed tomography-computed tomography thyroid bed uptake and the efficacy of radioactive iodine adjuvant therapy for papillary thyroid cancer

Introduction

In recent years, there has been a significant increase in the incidence of thyroid cancer worldwide, with a tendency for younger individuals to be affected (1). Thyroid cancer is classified into differentiated thyroid cancer (DTC), anaplastic thyroid cancer (ATC), poorly differentiated thyroid cancer (PDTC), and medullary thyroid carcinoma (MTC) based on tumor origin and differentiation. DTC includes subtypes such as papillary thyroid cancer (PTC), thyroid follicular cancer (FTC), eosinophil cancer (OCA), and differentiated high-grade thyroid cancer (DHGTC) (2). PTC is the most common subtype, accounting for 85–90% of all thyroid cancers. The treatment approaches for DTC mainly include surgical therapy, radioactive iodine (RAI) therapy, and thyroid-stimulating hormone (TSH) suppression therapy. RAI therapy plays a crucial role in the comprehensive treatment following total thyroidectomy for PTC and FTC. The goals of RAI therapy include remnant ablation, adjuvant therapy, or treatment for persistent disease (3). RAI adjuvant therapy aims to improve disease-free survival by potentially eliminating suspicious but unconfirmed residual diseases, especially in patients at high risk of disease recurrence (1).

Despite DTC being characterized by low malignancy, a low mortality rate, and a long survival period, it significantly impacts patients’ quality of life and health. Therefore, standardized diagnosis, therapy, and follow-up are crucial. Serum thyroglobulin (Tg) level is a specific indicator reflecting the burden of thyroid tissue in the body, including normal tissue and the primary and metastatic tumors of DTC. Changes in serum Tg levels are often earlier and more sensitive than are imaging structural lesions, serving as an important indicator to assess tumor residue, recurrence, or metastasis. It not only reflects the postoperative disease status of DTC but can also be used to evaluate the risk of initial or dynamic recurrence and the response to therapy (4). According to the 2015 management guidelines of the American Thyroid Association (ATA), patients with low-risk and intermediate-risk DTC who have undergone remnant ablation or adjuvant therapy and exhibit negative outcomes on cervical ultrasound should have their serum Tg levels measured between 6–18 months while on thyroxine therapy via a sensitive Tg measurement (<0.2 ng/mL) or stimulated thyroglobulin (sTg) to confirm disease-free status (3). However, the presence of Tg antibodies (TgAb) can cause a decrease in serum Tg values and even lead to false negatives when immunological methods are used to measure serum Tg levels, thereby reducing the sensitivity of Tg for disease monitoring (5).

In recent years, single-photon emission computed tomography-computed tomography (SPECT/CT) has been proven to be capable of accurately quantifying the radioactive isotope uptake with the development of advanced software (6). These software packages allow for the measuring of quantitative parameters such as standardized uptake values (SUV) and absolute radioactivity concentration at uptake sites (7-9). For instance, a study using SPECT/CT uptake analysis identified the BRAF V600E mutation in PTC carcinoma as an independent factor that diminishes the effectiveness of postsurgical iodine-131 (I-131) therapy (10). Moreover, several recent studies have shown that the quantitative parameters of I-131 SPECT/CT may be valuable for predicting the efficacy of RAI therapy (11,12). However, few quantitative reports are available regarding I-131 adjuvant therapy, and the influencing factors of quantitative parameters have not been fully discussed. The aim of this study was to analyze the factors influencing the quantitative parameters [maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), and percent injected dose (%ID)] of I-131 SPECT/CT uptake in the thyroid bed and to investigate their correlation with the efficacy of RAI adjuvant therapy using quantitative analysis of I-131 SPECT/CT images obtained 3 days after I-131 adjuvant therapy. We present this article in accordance with the STROBE reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-23-1723/rc).

Methods

This retrospective cohort study included 107 patients with PTC who underwent RAI adjuvant therapy at the Second Hospital of Dalian Medical University from June 2020 to January 2023. Only patients with PTC were included in this study, and patients with aggressive subtypes of PTC (tall cell subtype, columnar cell subtype, hobnail subtype) were excluded since they are less sensitive to I-131 treatment. All patients underwent total thyroidectomy prior to receiving RAI adjuvant therapy. Patients were classified according to the 2015 ATA risk stratification system (3), and those with a low risk of recurrence were excluded because RAI is not recommended for these patients in the recent guidelines (3). A summary of the patients’ characteristics is presented in Table 1. All patients were followed up at the Second Hospital of Dalian Medical University. This study was conducted in accordance with the Declaration of Helsinki (as revised in 2013) and was approved by the Ethics Committee of The Second Hospital of Dalian Medical University. The requirement for individual consent for this retrospective analysis was waived.

All patients followed a low-iodine diet for 4 weeks before RAI adjuvant therapy to reduce the competitive inhibitory effect of stable iodine on I-131. Additionally, patients underwent thyroid hormone withdrawal, which involved discontinuing thyroxine for 3 weeks to achieve a serum TSH concentration >30 mIU per liter, as required for RAI pretherapy (3).

All patients in this study received an adjuvant therapeutic dose of 5.50 GBq, as per the recommended dose ranges in China (13). I-131 was purchased from Chengdu Xinke Pharmaceutical Co.

The sTg was measured 1 day before RAI adjuvant therapy. As in previous studies (14), an I-131 whole-body scan and SPECT/CT were conducted to visualize high-uptake lesions in the thyroid bed 3 days after RAI adjuvant therapy. All lesions with high uptake were located in the thyroid bed of I-131 SPECT/CT. Cases of occasional lymph node or distant metastasis detected in scintigraphy after adjuvant therapy were excluded.

The SPECT/CT system was calibrated, and the system sensitivity was established at 159 cnt/min/uCi for calculating the quantitative parameters. System sensitivity denotes the conversion factor between radioactivity and counts per second. Three days after RAI adjuvant therapy, an I-131 whole-body scan and SPECT/CT imaging were conducted using a SPECT/CT system (GE HealthCare, IL, USA) equipped with a high-energy and high-resolution parallel hole collimator. The photo peak and energy window were set at 365%±10% keV. A planar whole-body scan was acquired with the patient in the supine position in both anterior and posterior views, with the parameters being a matrix size of 256×1,024, a speed of 13.3 cm/min, and a full width at half-maxima (FWHM) of 2.21 mm. Subsequently, SPECT images were immediately obtained after the whole-body scan under the following settings: matrix size 128×128; zoom 1.0; dual-probe acquisition; and probe rotation of 180°, 6°/frame, and 16 s/frame. CT images were captured under the following settings: a tube voltage of 120 kV, a tube current of 210 mA, a rotation time of 0.6 s, a table speed of 13.75 mm/rotation, a slice thickness of 3.75 mm, a pitch of 1.375:1, and a matrix size of 512× 512. No contrast agent was administered.

SPECT image reconstruction was performed by employing the ordered subset expectation maximization algorithm (OSEM) with 2 iterations and 10 subsets. Additional corrections, including scattering correction, sensitivity recovery, and attenuation correction based on CT data, were also performed (6).

Q.Metrix imaging quantitative software (GE HealthCare) was used for the automatic segmentation of three-dimensional volume of interest (VOI) of thyroid residues through 0.4 nuclear medicine (NM) thresholds, meaning that 40% of the maximum voxel was included for the determination of the region of interest (ROI). The NM thresholds referred to the threshold used for nuclear medicine image processing. By setting different thresholds, it could help distinguish tissues or structures and perform quantitative measurements on ROI. For most patients, the value of NM threshold was 0.4, but a few patients had the values adjusted to 0.2 to ensure that the halation observed in thyroid uptake in SPECT/CT included all lesions but excluded any halation extending outside the body. The software measured the SUVmax, SUVmean, %ID, and the volume of thyroid remnant VOIs (6). A typical graph is shown in Figure 1. SUV referred to the ratio of the total radioactive uptake in the VOIs to the total administered radioactive dose per unit of body weight. The %ID referred to the ratio of the total radioactivity of VOIs to the total administered radioactivity (6).

Figure 1 Therapeutic I-131 SPECT/CT images after RAI adjuvant therapy. The quantitative parameters of I-131 SPECT/CT thyroid bed uptake included an SUVmax of 6.96 g/mL, an SUVmean of 2.98 g/mL, and an %ID of 3.00%. The threshold value was 0.4 nm. CT, computed tomography; NM, nuclear medicine; MIP, maximum intensity projection; I-131 SPECT/CT, iodine-131 single-photon emission computed tomography-computed tomography; RAI, radioactive iodine; SUVmax, maximum standardized uptake value; SUVmean, mean standardized uptake value; %ID, percent injected dose.

Both inhibitory Tg and TgAb were measured 6 months after I-131 administration to evaluate the efficacy of RAI adjuvant therapy, and cervical ultrasound and chest CT examinations were also conducted. The threshold for TgAb-negative status is a level less than 40 IU/mL (15,16). Successful therapy was defined as inhibitory Tg <0.2 ng/mL with negative TgAb and negative imaging examination 6 months after RAI adjuvant therapy (3). Imaging examination included chest CT and neck ultrasound. Cases that did not meet these criteria were considered unsuccessful. The relationship between the quantitative parameters and the treatment efficacy, along with the potential influencing factors, was analyzed.

Statistical analyses were performed using SPSS 25.0 software (IBM Corp., NY, USA). Data with nonnormal distribution are expressed as the median and interquartile range (IQR). Differences in quantitative parameters between groups were assessed using the Mann-Whitney test. Spearman correlation analysis was employed to examine the associations between quantitative parameters and inhibitory Tg levels at 6 months after RAI adjuvant therapy, sTg, TgAb, and the volume of thyroid remnant VOIs. To identify predictive factors for the efficacy of RAI adjuvant therapy, binary logistic regression analysis was performed. Separate logistic regression models were constructed for SUVmax, SUVmean, and %ID to address multicollinearity (the value of %ID was increased by a factor of 100). Receiver operating characteristic (ROC) curves were used to assess the predictive accuracy of the quantitative parameters for estimating the efficacy of RAI adjuvant therapy. A P value <0.05 was considered statistically significant.

Results

Figure 2 shows significant differences in the distribution of quantitative parameters among three groups: the group with inhibitory Tg <0.2 ng/mL and negative for TgAb, the group with inhibitory Tg <0.2 ng/mL and positive for TgAb, and the group with inhibitory Tg ≥0.2 ng/mL. The quantitative parameters from the inhibitory Tg ≥0.2 ng/mL group [SUVmax: median 30.32 g/mL, IQR 13.41–58.36 g/mL; SUVmean: median 8.15 g/mL, IQR 4.38–22.81 g/mL; %ID: median 13.00%, IQR 6.00–20.00%] were significantly higher than the other two groups, and the difference was statistically significant (SUVmax: H=24.851; SUVmean: H=21.899; %ID: H=26.632; all P values <0.001). The quantitative parameters (SUVmax, SUVmean, and %ID) obtained from I-131 SPECT/CT showed a significant positive correlation with inhibitory Tg levels 6 months after RAI adjuvant therapy, with correlation coefficients of 0.464, 0.430, and 0.466, respectively (all P values <0.001). Moreover, the SUVmax, SUVmean, and %ID had significant positive correlations with sTg (Figure 3), with correlation coefficients of 0.610, 0.592, and 0.591, respectively (all P values <0.001). Additionally, the volume of thyroid remnant VOIs showed positive correlations with the quantitative parameters (SUVmax, SUVmean, and %ID), sTg, and 6-month Tg levels after RAI adjuvant therapy, with correlation coefficients of 0.356 (P<0.001), 0.229 (P=0.02), 0.521 (P<0.001), 0.238 (P=0.02), and 0.271 (P=0.005), respectively.

Figure 2 Comparison of SPECT/CT uptake parameters among the inhibitory Tg <0.2 ng/mL and TgAb-negative group, the inhibitory Tg ≥0.2 ng/mL group, and the inhibitory Tg <0.2 ng/mL and TgAb-positive group. (A) Comparison of SUVmax and SUVmean among the inhibitory Tg <0.2 ng/mL and TgAb-negative group, the inhibitory Tg ≥0.2 ng/mL group, and the inhibitory Tg <0.2 ng/mL and TgAb-positive group. (B) Comparison of %ID among the inhibitory Tg <0.2 ng/mL and TgAb-negative group, the inhibitory Tg ≥0.2 ng/mL group, and the inhibitory Tg <0.2 ng/mL and TgAb-positive group. *, P<0.001. The y-axis represents the unit of the corresponding variable, the unit of SUV is g/mL, and the %ID is unitless. SUVmax, maximum standardized uptake value; SUVmean, mean standardized uptake value; %ID, percent injected dose; Tg, thyroglobulin; TgAb, thyroglobulin antibody. SPECT/CT, single-photon emission computed tomography-computed tomography.

Figure 3 Scatter plots of significant positive correlation between quantitative parameters SUVmax (A), SUVmean (B), and %ID (C) with correlated coefficients of 0.610, 0.592 and 0.591, respectively (all P values <0.001). sTg, thyrotropin-stimulated thyroglobulin; SUVmax, maximum standardized uptake value; SUVmean, mean standardized uptake value; %ID, percent injected dose.

Figure 2 shows the quantitative parameters from the groups with inhibitory Tg <0.2 ng/mL and positive for TgAb (SUVmax: median 7.51 g/mL, IQR 3.27–26.41 g/mL; SUVmean: median 3.01 g/mL, IQR 1.17–10.80 g/mL; %ID: median 5.00%, IQR 1.00–8.00%) were higher than those from the group with inhibitory Tg <0.2 ng/mL and negative for TgAb (SUVmax: median 6.14 g/mL, IQR 2.34–13.82 g/mL; SUVmean: median 2.02 g/mL, IQR 0.89–4.93 g/mL; %ID: median 2.00%, IQR 1.00–4.00%), but the difference was not statistically significant (SUVmax: Z=−1.128, P=0.26; SUVmean: Z=−1.348, P=0.18; %ID: Z=−1.599, P=0.11). When participants were grouped based on their TgAb expression, the quantitative parameters from the TgAb-positive group (SUVmax: median 11.12 g/mL, IQR 3.32–29.89 g/mL; SUVmean: median 3.04 g/mL, IQR 1.34–11.34 g/mL; %ID: median 5.00%, IQR 1.00–13.00%) were higher than those from the TgAb-negative group (SUVmax: median 9.71 g/mL, IQR 3.21–24.90 g/mL; SUVmean: median 2.78 g/mL, IQR 0.98–6.71 g/mL; %ID: median 3.00%, IQR 1.00–10.75%), but the difference was not statistically significant (SUVmax: Z=−0.344, P=0.73; SUVmean: Z=−0.344, P=0.60; %ID: Z=−0.775, P=0.44). Moreover, TgAb was not significantly correlated with the I-131 SPECT/CT parameters of SUVmax (P=0.79), SUVmean (P=0.70), and %ID (P=0.57). The above results indicated that quantitative parameters were correlated with Tg but not with TgAb.

As illustrated in Figure 4 and Table 2, the quantitative parameters from the successful therapy group (SUVmax: median 6.15 g/mL, IQR 2.34–13.80 g/mL; SUVmean: median 2.02 g/mL, IQR 0.89–4.93 g/mL; %ID: median 2.00%, IQR 1.00–4.00%) were lower than those from the unsuccessful therapy group (SUVmax: median 19.03 g/mL, IQR 5.31–45.10 g/mL; median: SUVmean 4.64 g/mL, IQR 2.07–19.05 g/mL; %ID: median 8.00%, IQR 3.00–18.00%), with these differences representing a significant difference (SUVmax: Z=−3.755; SUVmean: Z=−3.671; %ID: Z=−4.070; all P values <0.001).

Figure 4 Comparison of SPECT/CT uptake parameters between successful and unsuccessful therapy group. (A) Comparison of SUVmax and SUVmean between the successful and unsuccessful therapy group. (B) Comparison of %ID between the successful and unsuccessful therapy group. *, P<0.001. The y-axis represents the unit of the corresponding variable, the unit of SUV is g/mL, and the %ID is unitless. SUVmax, maximum standardized uptake value; SUVmean, mean standardized uptake value; %ID, percent injected dose; SPECT/CT, single-photon emission computed tomography-computed tomography.

Table 3 presents the results of binary logistic regression analysis, which revealed that unsuccessful RAI adjuvant therapy could be predicted by SUVmax [odds ratio (OR) =1.045; 95% confidence interval (CI): 1.018–1.075; P=0.001], SUVmean (OR =1.130; 95% CI: 1.048–1.217; P=0.001), %ID (OR =1.092; 95% CI: 1.032–1.155; P=0.002), and sTg (OR =1.072; 95% CI: 1.019–1.129; P=0.008). The ROC curve analysis results in Figure 5 demonstrate that SUVmax, SUVmean, and %ID had good predictive efficacy for unsuccessful RAI adjuvant therapy, with AUC values of 0.711 (95% CI: 0.612–0.809), 0.706 (95% CI: 0.608–0.804), and 0.727 (95% CI: 0.630–0.825), respectively. The optimal thresholds for identifying unsuccessful treatment were an SUVmax of 9.71 g/mL with a sensitivity of 68.6% and a specificity of 66.1%, an SUVmean of 2.73 g/mL with a sensitivity of 68.6% and a specificity of 62.5%, and an ID% of 3.5% with a sensitivity 70.6% and a specificity 73.2%. We further found that the predictive value of quantitative parameters for efficacy would further increase only in cases where TgAb was negative, with AUC values of 0.829 (95% CI: 0.734–0.924), 0.805 (95% CI: 0.705–0.905), and 0.826 (95% CI: 0.726–0.925) for SUVmax, SUVmean, and %ID, respectively (all P values <0.001).

Figure 5 ROC curve analysis of the I-131 SPECT/CT uptake parameters. SUVmax, SUVmean, and %ID to predict the unsuccessful therapy of RAI therapy. ROC, receiver operating characteristic; SUVmax, maximum standardized uptake value; SUVmean, mean standardized uptake value; %ID, percent injected dose; I-131 SPECT/CT, iodine-131 single-photon emission computed tomography-computed tomography; RAI, radioactive iodine.

Discussion

SPECT/CT imaging has gradually become widely accepted in the evaluation of DTC due to its ability to accurately locate and characterize abnormal lesions with accumulated radioactive nuclides, which affects staging, risk stratification, and clinical therapy (17). With the advancement of imaging technology, quantitative parameters of SPECT/CT have become vital imaging markers for disease diagnosis (18), therapy response evaluation (19,20), therapy guidance (9,21), and disease monitoring (22,23). However, research on the quantitative parameters of SPECT/CT imaging 3 days after RAI adjuvant therapy has been relatively limited. Recently, studies have found that these parameters are associated with the efficacy of ablation therapy, and %ID was found to be a predictor of the successful outcome of ablation therapy in patients with DTC (6). Additionally, quantitative evaluation could serve as a predictive indicator for the disappearance of RAI accumulation in the thyroid bed after RAI adjuvant therapy (14).

In this study, we found that there was a correlation between the quantitative parameters of I-131 SPECT/CT of the thyroid bed and Tg but not TgAb. It is widely accepted that serum Tg level reflects the amount of thyroid tissue, making it a valuable tumor marker for patients with DTC who have undergone total thyroidectomy and RAI adjuvant therapy (24). The predictive value of postoperative Tg levels could be affected by various factors, with the most important factor being the presence of TgAb. In the early postoperative stage, approximately 25% of patients with DTC may have significantly altered Tg levels due to the presence of TgAb, which is often associated with coexisting thyroid autoimmune diseases (24-26). In this study, we grouped patients based on the combination of inhibitory Tg and TgAb levels. We found that the quantitative parameters (SUVmax, SUVmean, and %ID) of the inhibitory Tg ≥0.2 ng/mL group were significantly higher than those of the group with inhibitory Tg <0.2 ng/mL and positive for TgAb and the group with inhibitory Tg <0.2 ng/mL and negative for TgAb, indicating significant statistical differences. Additionally, both sTg and inhibitory Tg at 6 months after RAI were positively correlated with SUVmax, SUVmean, and %ID. Interestingly, we also found that the quantitative parameters of the TgAb-positive group were not statistically different from those of the TgAb-negative group, and the quantitative parameters obtained from I-131 SPECT/CT did not correlate significantly correlate with TgAb. Based on this, we inferred that the parameters related to the uptake in the thyroid bed were only correlated with Tg levels and not influenced by TgAb. These findings suggest that unlike Tg levels, the quantitative parameters (SUVmax, SUVmean, and %ID) of I-131 SPECT/CT thyroid bed uptake are not influenced by the presence of TgAb. Considered in tandem with the high efficacy of I-131 therapy in the low-uptake group, our results suggest that the quantitative parameters of the I-131 SPECT/CT thyroid bed can be used as early and sensitive indicators of risk stratification and prognostic evaluation. This supports the potential usefulness of these parameters in the evaluation of patients with DTC, regardless of their TgAb status. The correlation was the same for the TgAb-positive and -negative patients and could be applied for both patient types.

In our evaluation of treatment efficacy using serological indicators and imaging modalities, we found that the quantitative parameters (SUVmax, SUVmean, and %ID) of I-131 SPECT/CT thyroid bed uptake in the unsuccessful therapy group were significantly higher than those in the successful therapy group. Furthermore, these parameters were identified as predictive factors for the unsuccessful therapy of RAI adjuvant therapy, especially when TgAb was negative, which is different from the findings of previous research conducted by Konishi et al. (14). In their study, they found that the uptake parameters of SUV and kBq/mL were lower in the not-disappeared-uptake group than in the disappeared-uptake group after RAI therapy. They proposed that quantitative evaluation could serve as predictive indicators for the disappearance of RAI accumulation in the thyroid bed. However, a limited number of patients were enrolled in that study, and the patients’ urine iodine levels were not evaluated before I-131 therapy. A different I-131 dose (diagnostic dose or therapeutic dose) was used in the evaluation of therapy efficacy in the study by Konishi et al., which might have influenced the visualization of the thyroid tissue. Another study by Zhang et al. also found that the quantitative parameters (SUVmax, SUVmean, and %ID) in the unsuccessful group were significantly lower compared to those in the successful group and found that %ID could be used as a predictive factor for successful ablation (6). However, only 15 patients were included in the unsuccessful ablation group in Zhang et al.’s study. Moreover, the influence of the volume of the thyroid remnant and TgAb was not taken into consideration in either of these two studies.

In our study, we observed a positive correlation between quantitative parameters and the volume of the thyroid remnant VOIs. This finding is consistent with a previous phantom study (27) and a proof-of-concept study which suggested that lesion shape and size could influence quantitative parameters (28). The influence of volume to the quantitative parameters might be more apparent when only a small amount of thyroid remnant remained after total thyroidectomy. This could explain the higher quantitative parameters observed in the unsuccessful therapy group, as higher SUV and %ID indicate more residual thyroid tissue and less effective therapy of RAI therapy (29). Furthermore, this study also found a positive correlation between the quantitative parameters of I-131 SPECT/CT and sTg levels, supporting the relationship between quantitative parameters and remnant volume. High SUV and sTg level could potentially be used as predictive factors for unsuccessful therapy after RAI therapy. First, as previous studies have proposed, quantitative parameters could reflect the degree of residual thyroid uptake of RAI and the kinetic characteristics (6). Second, our results suggest new possibility that the quantitative parameters may also reflect the amount of residual thyroid to some extent. Higher values of quantitative parameters indicated a larger amount of residual thyroid tissue, which implied a lower success rate of RAI therapy. However, the relationship between uptake parameters and the efficiency of RAI therapy requires further investigation.

Despite its promising findings, this study has several limitations that should be discussed. First, the efficacy of RAI therapy was determined solely based on serological indicators, chest CT, and ultrasound examination, which may not provide a complete evaluation. A few studies used diagnostic I-131 whole-body scans in their evaluation, which could provide additional information in some cases (6,14). Second, we employed a retrospective design with a limited number of cases, which could reduce the generalizability of the conclusions. Larger studies with a greater number of follow-up cases are needed to further evaluate the efficacy of RAI therapy. Finally, although various corrections were applied during image reconstruction, further exploration is still required to determine the reliability of quantitative parameters using imaging analysis software for the thyroid bed.

Conclusions

Our findings suggest that the quantitative parameters (SUVmax, SUVmean, and %ID) of I-131 SPECT/CT thyroid bed uptake can serve as useful tools in predicting therapy outcomes following RAI therapy, especially when patients are negative for TgAb. The correlation between these parameters and Tg levels support their potential usefulness in evaluating residual thyroid tissue and treatment efficacy. Furthermore, the independence of these parameters from TgAb status points to the practicability in a broader patient population. However, further research with larger sample sizes and comprehensive evaluation protocols is needed to validate these findings and to fully characterize the relationship between quantitative parameters and therapy outcome in patients with DTC.

Acknowledgments

Funding: This work was supported by the 1 + X Program of the Second Affiliated Hospital of Dalian Medical University (No. 2022LCJSZD03).

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-23-1723/rc

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-1723/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 (as revised in 2013) and was approved by the Ethics Committee of The Second Hospital of Dalian Medical University. The requirement for individual consent in this retrospective analysis was waived.

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/.

References

1. Francis GL, Waguespack SG, Bauer AJ, Angelos P, Benvenga S, Cerutti JM, Dinauer CA, Hamilton J, Hay ID, Luster M, Parisi MT, Rachmiel M, Thompson GB, Yamashita SAmerican Thyroid Association Guidelines Task Force. Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid 2015;716-59. [Crossref] [PubMed]
2. Baloch ZW, Asa SL, Barletta JA, Ghossein RA, Juhlin CC, Jung CK. LiVolsi VA, Papotti MG, Sobrinho-Simões M, Tallini G, Mete O. Overview of the 2022 WHO Classification of Thyroid Neoplasms. Endocr Pathol 2022;33:27-63. [Crossref] [PubMed]
3. Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, Pacini F, Randolph GW, Sawka AM, Schlumberger M, Schuff KG, Sherman SI, Sosa JA, Steward DL, Tuttle RM, Wartofsky L. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid 2016;26:1-133. [Crossref] [PubMed]
4. d'Herbomez M, Lion G, Béron A, Wémeau JL, DoCao C. Advances in thyroglobulin assays and their impact on the management of differentiated thyroid cancers. Ann Biol Clin (Paris) 2016;74:21-7. [Crossref] [PubMed]
5. Loh TP, Chong HW, Kao SL. Thyroglobulin and thyroglobulin autoantibodies: inter-pret with care. Endocrine 2014;46:360-1. [Crossref] [PubMed]
6. Zhang Q, Xu W. Correlation analysis of I-131 SPECT/CT uptake parameters with the success ablation treatment of thyroid remnant in patients with low-intermediate-risk differentiated thyroid cancer. Nucl Med Commun 2022;43:1051-7. [Crossref] [PubMed]
7. Dickson JC. Quantitative SPECT: a survey of current practice in the UK Nuclear Medicine Community. Nucl Med Commun 2019;40:986-94. [Crossref] [PubMed]
8. Bailey DL, Willowson KP. An evidence-based review of quantitative SPECT imaging and potential clinical applications. J Nucl Med 2013;54:83-9. [Crossref] [PubMed]
9. Dong F, Li L, Bian Y, Li G, Han X, Li M, Liu J, Xue Y, Li Y, Hu Y, Tan J. Standardized Uptake Value Using Thyroid Quantitative SPECT/CT for the Diagnosis and Evaluation of Graves' Disease: A Prospective Multicenter Study. Biomed Res Int 2019;2019:7589853. [Crossref] [PubMed]
10. Domínguez-Ayala M, Mínguez-Gabiña P, Paja-Fano M, Bilbao-González A, Expósito-Rodríguez A, Rodeño-Ortiz de Zarate E. The role of BRAF V600E mutation in post-surgical 131I therapy in papillary thyroid carcinoma: a study based on SPECT-CT uptake analysis. Q J Nucl Med Mol Imaging 2023;67:83-92. [Crossref] [PubMed]
11. Giovanella L, Clark PM, Chiovato L, Duntas L, Elisei R, Feldt-Rasmussen U, Leenhardt L, Luster M, Schalin-Jäntti C, Schott M, Seregni E, Rimmele H, Smit J, Verburg FA. Thyroglobulin measurement using highly sensitive assays in patients with differentiated thyroid cancer: a clinical position paper. Eur J Endocrinol 2014;171:R33-46. [Crossref] [PubMed]
12. Chen L, Wu W, Tian Y, Zeng Y, Hou C, Zhu H, Zheng K, Zhang Y, Gao Y, Peng B, Yang S, Wang X, Ning S, Liao Y, Lin H, Shi K, Li X, Chen WX. Thyroid Function and Anti-thyroid Antibodies in Pediatric Anti-NMDAR Encephalitis. Front Neurol 2021;12:707046. [Crossref] [PubMed]
13. Chinese Society of Endocrinology, Thyroid and Metabolism Surgery Group of the Chinese Society of Surgery, China Anti-Cancer Association, Chinese Association of Head and Neck Oncology, Chinese Society of Nuclear Medicine, China Anti-Cancer Association. Guidelines for the diagnosis and management of thyroid nodules and differentiated thyroid cancer (Second edition). Chin J Endocrinol Metab 2023;39:181-226.
14. Konishi K, Ishiba R, Ikenohira T, Asao T, Hirata M, Ohira K, Komatsu T, Sawada M, Tanahashi Y, Goshima S, Magata Y, Nakamura K. The relationship between the quantitative evaluation of thyroid bed uptake and the disappearance of accumulation in adjuvant radioactive iodine therapy for differentiated thyroid cancer. Ann Nucl Med 2021;35:159-66. [Crossref] [PubMed]
15. Liu Q, Yin M, Li G. Antithyroglobulin Antibody Variation During Follow-Up Has a Good Prognostic Value for Preoperative Antithyroglobulin Antibody-Positive Differentiated Thyroid Cancer Patients: A Retrospective Study in Southwest China. Front Endocrinol (Lausanne) 2021;12:774275. [Crossref] [PubMed]
16. Sun D, Zheng X, He X, Huang C, Jia Q, Tan J, Zheng W, Li N, Wang P, Wang R, Liu M, Zhao L, Yuan S, Meng Z, Fan Y. Prognostic value and dynamics of antithyroglobulin antibodies for differentiated thyroid carcinoma. Biomark Med 2020;14:1683-92. [Crossref] [PubMed]
17. Lee SW. SPECT/CT in the Treatment of Differentiated Thyroid Cancer. Nucl Med Mol Imaging 2017;51:297-303. [Crossref] [PubMed]
18. Qi N, Meng Q, You Z, Chen H, Shou Y, Zhao J. Standardized uptake values of 99mTc-MDP in normal vertebrae assessed using quantitative SPECT/CT for differentiation diagnosis of benign and malignant bone lesions. BMC Med Imaging 2021;21:39. [Crossref] [PubMed]
19. Roque V, Jessop M, Pereira L, Gape P, Dizdarevic S, Sousa E, Carolino E. Bone scan index as metastatic bone disease quantifier and predictor of radium-223-dichloride biochemical response. Nucl Med Commun 2019;40:588-96. [Crossref] [PubMed]
20. Umeda T, Koizumi M, Fukai S, Miyaji N, Motegi K, Nakazawa S, Takiguchi T. Evaluation of bone metastatic burden by bone SPECT/CT in metastatic prostate cancer patients: defining threshold value for total bone uptake and assessment in radium-223 treated patients. Ann Nucl Med 2018;32:105-13. [Crossref] [PubMed]
21. De Laroche R, Simon E, Suignard N, Williams T, Henry MP, Robin P, Abgral R, Bourhis D, Salaun PY, Dubrana F, Querellou S. Clinical interest of quantitative bone SPECT-CT in the preoperative assessment of knee osteoarthritis. Medicine (Baltimore) 2018;97:e11943. [Crossref] [PubMed]
22. Dittmann H, Kaltenbach S, Weissinger M, Fiz F, Martus P, Pritzkow M, Kupferschlaeger J, la Fougère C. The Prognostic Value of Quantitative Bone SPECT/CT Before (223)Ra Treatment in Metastatic Castration-Resistant Prostate Cancer. J Nucl Med 2021;62:48-54. [Crossref] [PubMed]
23. Oya T, Ichikawa Y, Nakamura S, Tomita Y, Sasaki T, Inoue T, Sakuma H. Quantitative assessment of 99mTc-methylene diphosphonate bone SPECT/CT for assessing bone metastatic burden and its prognostic value in patients with castration-resistant prostate cancers: initial results in a single-center retrospective study. Ann Nucl Med 2023;37:360-70. [Crossref] [PubMed]
24. Giovanella L. Circulating biomarkers for the detection of tumor recurrence in the postsurgical follow-up of differentiated thyroid carcinoma. Curr Opin Oncol 2020;32:7-12. [Crossref] [PubMed]
25. Knappe L, Giovanella L. Life after thyroid cancer: the role of thyroglobulin and thyroglobulin antibodies for postoperative follow-up. Expert Rev Endocrinol Metab 2021;16:273-9. [Crossref] [PubMed]
26. Görges R, Maniecki M, Jentzen W, Sheu SN, Mann K, Bockisch A, Janssen OE. Development and clinical impact of thyroglobulin antibodies in patients with differentiated thyroid carcinoma during the first 3 years after thyroidectomy. Eur J Endocrinol 2005;153:49-55. [Crossref] [PubMed]
27. Lee J, Nam-Kung S, Kim JH, Park HH. Consideration of standardized uptake value (SUV) according to the change of volume size through the application of astonish TF reconstruction method. J Nucl Med Technol 2014;18:115-21.
28. Mosleh-Shirazi MA, Nasiri-Feshani Z, Ghafarian P, Alavi M, Haddadi G, Ketabi A. Tumor volume-adapted SUV(N) as an alternative to SUV(peak) for quantification of small lesions in PET/CT imaging: a proof-of-concept study. Jpn J Radiol 2021;39:811-23. [Crossref] [PubMed]
29. James DL, Ryan ÉJ, Davey MG, Quinn AJ, Heath DP, Garry SJ, Boland MR, Young O, Lowery AJ, Kerin MJ. Radioiodine Remnant Ablation for Differentiated Thyroid Cancer: A Systematic Review and Meta-analysis. JAMA Otolaryngol Head Neck Surg 2021;147:544-52. [Crossref] [PubMed]