Theranostic application of 64Cu/177Lu-labeled anti-Trop2 monoclonal antibody in pancreatic cancer tumor models

• Published in: European journal of nuclear medicine and molecular imaging 2022-12, Vol.50 (1), p.168-183
• Main Authors: Li, Cuicui, Liu, Jun, Yang, Xu, Yang, Qi, Huang, Wenpeng, Zhang, Mingyu, Zhou, Dandan, Wang, Rong, Gong, Jianhua, Miao, Qingfang, Kang, Lei, Yang, Jigang
• Format: Article
• Language: English
• Subjects: Antigens; Binding; Cancer; Cardiology; Cell surface; Evaluation; Flow cytometry; Glycoproteins; Heterogeneity; Imaging; Immunofluorescence; In vivo methods and tests; Lethality; Lutetium isotopes; Malignancy; Medical imaging; Medicine; Medicine & Public Health; Monoclonal antibodies; Nuclear Medicine; Oncology; Original Article; Orthopedics; Pancreatic cancer; Positron emission; Positron emission tomography; Radiochemistry; Radiolabelling; Radiology; Theragnostic; Tumor cell lines; Tumor suppression; Tumors; Western blotting
• ISSN: 1619-7070; 1619-7089; 1619-7089
• DOI: 10.1007/s00259-022-05954-y

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 64 Cu/ 177 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 64 Cu and 177 Lu radiolabeling respectively. ImmunoPET imaging and RIT studies were performed using 64 Cu-NOTA-hIMB1636 and 177 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 64 Cu-NOTA-hIMB1636 and 177 Lu-DOTA-hIMB1636 exceeded 95%. PET imaging showed gradually an accumulation of 64 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