64Cu Radiolabeled PDGFRβ-Targeting Affibody for PET Imaging in Pancreatic Cancer.

Pancreatic cancer is a malignant solid tumor that contains a significant number of cancer-associated fibroblasts (CAFs). Clinical trials have confirmed that CAF-targeted radionuclide therapy can suppress tumor growth and extend the survival of patients; therefore, quantifying CAFs by molecular imaging of CAF biomarkers is helpful for assessing disease progression and therapeutic responses of pancreatic cancer. In our previous study, we found that platelet-derived growth factor receptor beta (PDGFRβ) was highly expressed on various fibroblast cells, and a novel affibody (ZPDGFRβ) with highly specific binding to PDGFRβ had been developed. Herein, we verified the high expression of PDGFRβ on CAFs in pancreatic cancer tissues, and the ZPDGFRβ affibody was radiolabeled with 64Cu to obtain a [64Cu]Cu-NOTA-ZPDGFRβ conjugate with radiochemical purity higher than 95%. Biodistribution studies showed that tumor uptake of [64Cu]Cu-NOTA-ZPDGFRβ reached the peak of 7.28 ± 0.92 at 6 h postinjection, and the tumor-to-pancreas ratio continuously increased to reach the peak of 25.9 ± 8.18 at 24 h postinjection. Positron emission tomography (PET) imaging with [64Cu]Cu-NOTA-ZPDGFRβ showed ideal tumor uptake and imaging capability in mice bearing both subcutaneous xenografts and in situ grafts. Our results demonstrated that the [64Cu]Cu-NOTA-ZPDGFRβ conjugate could be applied as a promising PDGFRβ-targeted radiotracer for PET imaging of pancreatic cancer.