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

Abstract

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 (Z_PDGFRβ) 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 Z_PDGFRβ affibody was radiolabeled with ⁶⁴Cu to obtain a [⁶⁴Cu]Cu-NOTA-Z_PDGFRβ conjugate with radiochemical purity higher than 95%. Biodistribution studies showed that tumor uptake of [⁶⁴Cu]Cu-NOTA-Z_PDGFRβ 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-Z_PDGFRβ 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-Z_PDGFRβ conjugate could be applied as a promising PDGFRβ-targeted radiotracer for PET imaging of pancreatic cancer.