Investigation of 47Sc-Radiolabeled PDGFRβ-Targeted Affibody in SPECT Imaging and Radiotherapy of Pancreatic Cancer

Abstract Pancreatic cancer is a malignant solid tumor that contains a large number of cancer-associated fibroblasts (CAFs). Therefore, it is crucial to evaluate the disease progression of the tumor and plan radionuclide therapy through the molecular imaging of CAF biomarkers. Platelet-derived growth factor receptor β (PDGFRβ) was found that it was highly expressed on fibroblasts, and a specific affinity probe ZPDGFRβ that binds to PDGFRβ was successfully developed. In this study, ⁴⁷Sc was used to label the affibody targeting PDGFRβ to explore its distribution characteristics in pancreatic cancer and the therapeutic effect of radionuclides. ⁴⁷Sc was produced via thermal neutron irradiated enriched ⁴⁶Ca with radionuclide purity over 99.9%. The ZPDGFRβ affibody was radiolabeled by ⁴⁷Sc to obtain a ⁴⁷Sc-DOTA-ZPDGFRβ conjugate with radiochemical purity higher than 99%. Biodistribution studies showed that tumor uptake of ⁴⁷Sc-DOTA-ZPDGFRβ reached 4.57 ± 2.12 at 1h post-injection, and 4.00 ± 0.71 at 96h postinjection. However, the uptake by the liver and the kidneys reached 10.44 ± 3.19, 49.90 ± 8.89 respectively at 1h postinjection, and then it drops to 2.20 ± 1.04 and 2.60 ± 0.27. Single-Photon Emission Computed Tomography (SPECT) imaging indicated specific uptake of ⁴⁷Sc-DOTA-ZPDGFRβ in PANC-2 pancreatic tumors. Therapeutic experiments revealed that ⁴⁷Sc has an effective anti-tumor ability similar to ¹⁷⁷Lu. Our research results indicated that the ⁴⁷Sc-DOTA-ZPDGFRβ conjugate exhibited remarkable targeting efficacy as a PDGFRβ-targeted radiotracer in SPECT imaging and also demonstrated favorable radiotherapy capabilities. SPECT imaging of ⁴⁷Sc ions also revealed the characteristic distribution patterns in cardiac, aortic, and hepatic regions, held significant implications for future pharmaceutical development and radiation side-effect prediction.