uPAR Immuno-PET in Pancreatic Cancer, Aging, and Chemotherapy-Induced Senescence

uPAR 免疫 PET 在胰腺癌、衰老和化疗诱导衰老中的作用

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作者:Edwin C Pratt, Riccardo Mezzadra, Amanda Kulick, Spencer Kaminsky, Zachary V Samuels, Angelique Loor, Elisa de Stanchina, Scott W Lowe, Jason S Lewis

Conclusion

The use of radiolabeled uPAR-targeting antibodies provides a new antibody-based PET imaging candidate for pancreatic cancer imaging as well as chemotherapy-induced senescence.

Methods

Here, 2 antibodies against murine uPAR and human uPAR were developed as immuno-PET agents to noninvasively track uPAR antigen abundance.

Results

TP treatment increased cell uptake both in murine KPC cells and in human MiaPaCa2 cells. In vivo, subcutaneously implanted murine KPC tumors had high tumor uptake with the antimurine uPAR antibody independently of TP in young mice, yet uPAR uptake was maintained in aged mice on TP. Mice xenografted with human MiaPaCa2 tumors showed a significant increase in tumor uptake on TP therapy when imaged with the antihuman uPAR antibody. Imaging with either uPAR antibody was found to be more tumor-selective than imaging with [18F]FDG or [18F]F-DPA-714.

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