Evaluation of integrin alpha(v)beta(3)-targeted imaging for predicting disease progression in patients with high-risk differentiated thyroid cancer (using Tc-99m-3PRGD(2))

Background: High-risk differentiated thyroid cancer (DTC) needs effective early prediction tools to improving clinical management and prognosis. This cohort study aimed to investigate the prognostic impact of Tc-99m-PEG(4)-E[PEG(4)-c(RGDfK)](2) (Tc-99m-3PRGD(2)) SPECT/CT in high-risk DTC patients after initial radioactive iodine (RAI) therapy.Methods: Thirty-three patients with high-risk DTC were prospectively recruited; all patients underwent total thyroidectomy and received Tc-99m-3PRGD(2) SPECT/CT before RAI ablation. Follow-up was done with serological and imaging studies. The correlation between Tc-99m-3PRGD(2) avidity and remission rate for initial RAI therapy was evaluated using logistic regression analysis. The prognostic value of Tc-99m-3PRGD(2) SPECT/CT was evaluated by Kaplan-Meier curve and Cox regression analysis.Results: Tc-99m-3PRGD(2) avidity was significantly correlated with the efficacy of initial RAI ablation and an effective predictor for non-remission in high-risk DTC (OR = 9.36; 95% CI = 1.10-79.83; P = 0.041). Tc-99m-3PRGD(2) avidity was associated with poor prognosis in patients with high-risk DTC and an independent prognostic factor for shorter progression-free survival (PFS) (HR = 9.47; 95% CI = 1.08-83.20; P = 0.043). Survival analysis, which was performed between DTC patients with concordant (I-131 positive/Tc-99m-3PRGD(2) positive) and discordant (I-131 negative/Tc-99m-3PRGD(2) positive) lesions, indicated that patients with concordant lesions had significantly better PFS than those with discordant lesions (P = 0.022). Moreover, compared with repeated RAI, additional surgery or targeted therapy with multikinase inhibitors could lead to a higher rate of remission in Tc-99m-3PRGD(2)-positive patients with progressive disease.Conclusions: Tc-99m-3PRGD(2) SPECT/CT is a useful modality in predicting progression of the disease after initial RAI and guiding further treatment in high-risk DTC patients.