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 investigate the expression and distribution of FNDC5/Irisin in pancreatic cancer tissues and adjacent tissues, and to analyze its correlation with clinicopathological features. Methods: Collection of archived wax blocks from 64 patients diagnosed with pancreatic cancer after surgical treatment from January 2015 to December 2018 in the Department of Pathology, Affiliated Qingdao Municipal Hospital of Qingdao University, and 30 tissues collected intraoperatively from January 2016 to December 2018 Samples, all collected samples included tumor tissue and corresponding adjacent tissues (>2 cm from the tumor edge). Real-time quantitative PCR (qRT-PCR) and immunohistochemistry were used to detect the expression of FNDC5/Irisin mRNA and its positivity in pancreatic cancer tissues and adjacent tissues, and to analyze its relationship with clinicopathological features of pancreatic cancer. Results: qRT-PCR showed that the expression of FNDC5/Irisin mRNA in pancreatic cancer tissues was higher than that in the corresponding adjacent pancreatic tissues, the difference was statistically significant (P<0.05). The immunohistochemistry results showed that the positivity of FNDC5/Irisin in pancreatic cancer tissues was 59.4%, and the positivity of FNDC5/Irisin in adjacent tissues was 28.1%, and the positivity of FNDC5/Irisin in cancer tissues and adjacent pancreatic tissues was significantly different (P<0.05); the expression level of FNDC5/Irisin was not related with the gender, age, tumor size, degree of differentiation, and tumor stage.(P>0.05), but FNDC5/Irisin expression was associated with liver and lymph node metastasis (P<0.05). Conclusion The positivity of FNDC5/Irisin in pancreatic cancer tissues is significantly higher than that in adjacent pancreatic tissues, and it is correlated with liver and lymph node metastasis in pancreatic cancer.