Purpose: Pancreatic cancer is a malignant tumor with a high degree of malignancy, strong heterogeneity, and high lethality. Trop2 is a transmembrane glycoprotein associated with the occurrence, development, and poor prognosis of pancreatic cancer. This study aims to develop Cu/Lu-labeled anti-Trop2 monoclonal antibody (hIMB1636) for positron emission tomography (PET) imaging and radioimmunotherapy (RIT) application in pancreatic cancer tumor models.
Methods: The binding kinetics of hIMB1636 to Trop2 antigen was measured by Biolayer interferometry (BLI). Western blotting was used to screen the Trop2 expression of pancreatic cancer cell lines. Flow cytometry and cell immunofluorescence were used to evaluate the binding ability of hIMB1636 and Trop2 on the cell surface. hIMB1636 were conjugated with p-SCN-Bn-NOTA (NOTA) and DOTA-NHS-ester (DOTA) for Cu and Lu radiolabeling respectively. ImmunoPET imaging and RIT studies were performed using Cu-NOTA-hIMB1636 and Lu-DOTA-hIMB1636 in subcutaneous pancreatic cancer tumor models.
Results: hIMB1636 had a strong binding affinity to Trop2 according to the results of BLI. The T3M-4 cell line showed the strongest expression of Trop2 and specific binding ability of hIMB1636 according to the results of Western blotting, flow cytometry, and cell immunofluorescence. The radiochemical purity of Cu-NOTA-hIMB1636 and Lu-DOTA-hIMB1636 exceeded 95%. PET imaging showed gradually an accumulation of Cu-NOTA-hIMB1636 in T3M-4 tumor models. The maximum tumor uptake was 8.95 ± 1.07%ID/g (n = 4) at 48 h post injection (p.i.), which had significant differences with T3M-4-blocked and PaTu8988-negative groups (P < 0.001). The high-Lu-hIMB1636 group demonstrated the strongest tumor suppression with standardized tumor volume about 94.24 ± 14.62% (n = 5) at 14 days p.i., significantly smaller than other groups (P < 0.05). Ex vivo biodistribution and histological staining verified the in vivo PET imaging and RIT results.
Conclusions: This study demonstrated that Cu/Lu-labeled hIMB1636 could noninvasively evaluate the expression level of Trop2 and inhibit the Trop2-overexpressed tumor growth in pancreatic cancer tumor models. Further clinical evaluation and translation of Trop2-targeted drug may be of great help in the stratification and management of pancreatic cancer patients.
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http://dx.doi.org/10.1007/s00259-022-05954-y | DOI Listing |
Langenbecks Arch Surg
December 2024
Department of Surgery, TUM Universitätsklinikum Klinikum Rechts der Isar Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany.
Objective: Splenectomy is regularly performed in total and distal pancreatectomy due to technical reasons, lymph node dissection and radicality of the operation. However, the spleen serves as an important organ for competent immune function, and its removal is associated with an increased incidence of cancer and a worse outcome in some cancer entities (Haematologica 99:392-398, 2014; Dis Colon Rectum 51:213-217, 2008; Dis Esophagus 21:334-339, 2008). The impact of splenectomy in pancreatic cancer is not fully resolved (J Am Coll Surg 188:516-521, 1999; J Surg Oncol 119:784-793, 2019).
View Article and Find Full Text PDFJ Exp Clin Cancer Res
December 2024
The National Engineering Laboratory for Anti-Tumor Protein Therapeutics, Tsinghua University, Beijing, 100084, China.
Cell Signal
December 2024
Department of Maxillofacial and Otorhinolaryngology Oncology and Department of Head and Neck Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China; Tianjin Key Laboratory of Basic and Translational Medicine on Head & Neck Cancer, Tianjin, China; Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China. Electronic address:
Nerves are often overlooked as key components of the tumor microenvironment. However, the molecular mechanisms underlying the reciprocal interactions between tumors and nerves remain largely unknown. In this study, we analyzed data from The Cancer Genome Atlas (TCGA) and identified a significant association between DKK1 expression and poor prognosis, as well as a correlation between DKK1 expression and myeloid-derived suppressor cell (MDSC) infiltration in head and neck squamous cell carcinoma (HNSCC) and pancreatic ductal adenocarcinoma (PDAC), two cancer types characterized by pronounced tumor-nerve interactions.
View Article and Find Full Text PDFAnn Surg Oncol
December 2024
Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Background: Pancreatic enucleation is a reliable surgical method for treating benign and borderline pancreatic tumors; however, the incidence of postoperative pancreatic fistula (POPF) is high, especially when the tumor is close to the main pancreatic duct. This study aimed to reduce the incidence of pancreatic fistula by preoperative placement of pancreatic stents and to summarize our center's experience with this procedure.
Methods: From June 2020 to July 2023, patients diagnosed with benign or borderline pancreatic tumors at Renji Hospital were included.
BMC Surg
December 2024
Department of Surgery, Transplantation and Gastroenterology, Semmelweis University, Budapest, Hungary.
Background: Biliary leakage is a serious complication of hepato-pancreato-biliary operations, increasing morbidity and mortality, and challenging clinicians.
Objective: This study aims to evaluate the incidence of bilioenteric anastomotic leakage, treatment options, and their outcomes at a high-volume tertiary referral center.
Methods: A retrospective cohort study was conducted to analyze the outcomes of patients who underwent biliary anastomosis formation between 2016 and 2021.
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