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European Journal of Nuclear Medicine and Molecular Imaging

Published in:

05-09-2022 | Radioimmunotherapy | Original Article

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

Authors: Cuicui Li, Jun Liu, Xu Yang, Qi Yang, Wenpeng Huang, Mingyu Zhang, Dandan Zhou, Rong Wang, Jianhua Gong, Qingfang Miao, Lei Kang, Jigang Yang

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 1/2022

Abstract

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 ⁶⁴Cu/¹⁷⁷Lu-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 ⁶⁴Cu and ¹⁷⁷Lu radiolabeling respectively. ImmunoPET imaging and RIT studies were performed using ⁶⁴Cu-NOTA-hIMB1636 and ¹⁷⁷Lu-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 ⁶⁴Cu-NOTA-hIMB1636 and ¹⁷⁷Lu-DOTA-hIMB1636 exceeded 95%. PET imaging showed gradually an accumulation of ⁶⁴Cu-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-¹⁷⁷Lu-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 ⁶⁴Cu/¹⁷⁷Lu-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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Title: Theranostic application of 64Cu/177Lu-labeled anti-Trop2 monoclonal antibody in pancreatic cancer tumor models
Authors: Cuicui Li
Jun Liu
Xu Yang
Qi Yang
Wenpeng Huang
Mingyu Zhang
Dandan Zhou
Rong Wang
Jianhua Gong
Qingfang Miao
Lei Kang
Jigang Yang
Publication date: 05-09-2022
Publisher: Springer Berlin Heidelberg
Keywords: Radioimmunotherapy
Positron Emission Tomography
Pancreatic Cancer
Pancreatic Cancer
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 1/2022
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-022-05954-y

At a glance: The STEP trials

Springer Medicine

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

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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