Abstract
OBJECTIVE: In this prospective study, we aimed to investigate the factors associated with somatostatin receptor (SSTR) expression in patients with recurrent or metastatic differentiated thyroid cancer (DTC). METHODS: Patients with DTC scheduled for (131)I therapy at the study institution were enrolled. The inclusion criteria required at least one assessable lesion (≥ 1 cm). SSTR expression was assessed by (111)In-pentetreotide single-photon emission computed tomography/computed tomography (SPECT/CT), with Krenning scores of ≥ 2 considered positive. Fluorodeoxyglucose positron emission tomography (FDG PET) and post-(131)I therapy SPECT/CT were also evaluated. Quantitative evaluation was performed using standardized uptake values (SUV). Clinical factors were compared between SSTR-positive and SSTR-negative patients. Spearman’s correlation coefficient was calculated to evaluate the relationship between lesion size and SUVmax from (111)In-pentetreotide SPECT, FDG PET, and (131)I SPECT. Generalized estimating equations (GEEs) were utilized to identify predictors of SSTR positivity, accounting for within-patient correlation among multiple lesions. Furthermore, receiver operating characteristic (ROC) curves with clustered bootstrap resampling were used for evaluating the diagnostic performance of significant predictors. RESULTS: Fourteen patients with DTC (six male; median age, 70.5 years) were evaluated, and 31 lesions were assessed. High SSTR expression was observed in 28.6% (4/14) of patients and 51.6% (16/31) of lesions. SSTR positivity was associated with follicular histology, elevated thyroglobulin (Tg) levels, (131)I uptake, larger lesion size, and bone metastasis. Using GEEs accounting for intra-patient clustering, higher (131)I SUVmax was the strongest independent predictor of SSTR positivity (p < 0.001). ROC analysis demonstrated (131)I SUVmax yielded a high area under the curve of 0.93 (95% confidence interval: 0.65–1.00) for predicting SSTR positivity. SSTR SUVmax positively correlated with lesion size (ρ = 0.67), and (131)I SUVmax (ρ = 0.73). Although (18)F-FDG SUVmax moderately positively correlated with SSTR SUVmax (ρ = 0.49), it was not an independent predictor of SSTR positivity in GEE (p = 0.163). CONCLUSIONS: In this first study, high SSTR expression in Japanese patients with DTC was evaluated, demonstrating patients with follicular thyroid carcinoma, elevated Tg levels, larger tumor size, and positive (131)I uptake are more likely to have SSTR-positive lesions. These findings might support the development of novel SSTR-targeted radiopharmaceutical therapies for DTC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12149-026-02155-7.