Objective To evaluate the diagnostic efficiency of ⁹⁹Tc^m-sodium toluene sulfonate nicotinamide hydrazone PEGylated bicyclic arginine-glycine-aspatic acid peptide (abbreviation ⁹⁹Tc^m-3PRGD₂) SPECT/CT imaging to progressive radioiodine refractory differentiated thyroid cancer (RAIR-DTC) without iodine uptake.

Methods A total of 59 patients with RAIR-DTC who underwent ⁹⁹Tc^m-3PRGD2 SPECT/CT examination in Fujian Provincial Hospital from October 2019 to May 2022 were prospectively selected, including 17 males and 42 females, with a median age of 51 (28, 80) years. All patients underwent ⁹⁹Tc^m-3PRGD₂ SPECT/CT, among them, 22 patients were treated with a tyrosine kinase inhibitor (TKI), and 37 patients had thyroid-stimulating hormone (TSH) inhibition 13 patients underwent ¹⁸F-fluorodeoxyglucose (FDG) PET/CT within two weeks. Maximum standardized uptake value (SUV_max) of the lesion with the largest-length diameter in each patient was analyzed. The diagnostic efficiency of ⁹⁹Tc^m-3PRGD₂ SPECT/CT imaging was evaluated by receiver operating characteristic (ROC) curves analysis and was also used to calculate the SUV_max cut-off value of ⁹⁹Tc^m-3PRGD₂ SPECT/CT to assist in the detection of RAIR-DTC lesions. Using Pearson correlation analysis method to analyze the correlations between the target lesion (TL), stimulated thyroglobulin (sTg) levels and SUV_max. The relationships between the sTg levels, SUV_max and TL in RAIR-DTC patients before and after TKI treatment were analyzed by paired t test.

Results A total of 276 lesions from 59 RAIR-DTC patients were included in the analysis. These 59 lesions were compared before and after TKI treatment. The sensitivity and specificity of ⁹⁹Tc^m-3PRGD₂ SPECT/CT imaging for the diagnosis of RAIR-DTC lesions were 94.9% (95%CI: 90.7%–97.3%) and 88.7% (95%CI: 77.5%–95.0%), respectively. The ROC curves results showed that the cut-off value of SUV_max for RAIR-DTC lesions detected by ⁹⁹Tc^m-3PRGD₂ SPECT/CT imaging was 2.70. The results of the Pearson correlation analysis showed that the SUV_max of the target lesions was positively correlated with the sTg levels and TL (r=0.811, 0.635, both P=0.001). The paired t test results showed that SUV_max in RAIR-DTC lesions was significantly decreased before and after TKI treatment (t=11.027, P=0.001). Spearman correlation analysis showed that there was a positive correlation between ⁹⁹Tc^m-3PRGD₂ SPECT/CT imaging and ¹⁸F-FDG PET/CT imaging in detecting SUV_max of positive lesions (r=0.560, P=0.001). However, the results of ROC curves analysis did not show statistical significance in the diagnostic efficiency of ⁹⁹Tc^m-3PRGD₂ SPECT/CT imaging for RAIR-DTC lesions versus ¹⁸F-FDG PET/CT imaging (Z=0.312, P=0.753).

Conclusion ⁹⁹Tc^m-3PRGD₂ SPECT/CT imaging had high sensitivity and specificity in the diagnosis of progressive RAIR-DTC without iodine uptake, similar to ¹⁸F-FDG PET/CT.