Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as ¹⁷⁷Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of ¹⁷⁷Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, ¹⁷⁷Lu-LNC1010, for PRRT. In preclinical studies, ¹⁷⁷Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of ¹⁷⁷Lu-LNC1010 in patients with advanced/metastatic NETs. ¹⁷⁷Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of ¹⁷⁷Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two ¹⁷⁷Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.

Objective:To explore the correlation between the expression level of microRNA (miR)-206 and the expression levels of Wnt-1 and β-catenin in Wnt/β-catenin pathway in peripheral blood mononuclear cells of patients with hyperthyroidism.Methods:Using a prospective design, 79 patients with hyperthyroidism admitted to Wuwei City People's Hospital from January 2018 to June 2020 were selected as observation group, and 70 cases of healthy physical examination in Wuwei City People's Hospital from January 2019 to September 2020 were selected as control group. The observation group was treated with anti-thyroid drugs, and tambazole was orally taken 10-20 mg/d during the treatment period; after the serum thyroid hormone was normal, the dosage was reduced and maintained at 5-10 mg/d for 12 months. Quantitative real-time PCR (qRT-PCR) was used to detect the expression levels of miR-206, Wnt-1 and β-catenin mRNA in peripheral blood mononuclear cells in observation group before and after treatment and control group.Results:The expression level of miR-206 in peripheral blood mononuclear cells of observation group before treatment was lower than that of control group (0.28 ± 0.07 vs 0.79 ± 0.15), and the expression levels of Wnt-1 and β-catenin mRNA were higher than those of control group (6.75 ± 1.39 vs 2.23 ± 0.65, 5.83 ± 1.24 vs 3.21 ± 0.86, P < 0.05). The expression level of miR-206 (0.54 ± 0.13) in peripheral blood mononuclear cells of observation group after treatment was higher than that before treatment, and the expression levels of Wnt-1 and β-catenin mRNA (3.62 ± 1.08, 4.34 ± 1.16) were lower than those before treatment ( P < 0.05). The expression level of miR-206 in peripheral blood mononuclear cells of patients with hyperthyroidism was negatively correlated with the expression levels of Wnt-1 and β-catenin mRNA ( r = - 0.763, - 0.798, P < 0.05). Conclusions:The expression level of miR-206 in peripheral blood mononuclear cells of patients with hyperthyroidism is low, while the expression levels of Wnt-1 and β-catenin mRNA are high. The expression level of miR-206 is negatively correlated with the expression levels of Wnt-1 and β-catenin mRNA.