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

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 Z _PDGFRβ that binds to PDGFRβ was successfully developed. In this study, ⁴⁷ Sc was used to label the affibody targeting PDGFRβ to explore its distribution characteristics in pancreatic cancer and the therapeutic effect of radionuclides. ⁴⁷ Sc was produced via thermal neutron irradiated enriched ⁴⁶ Ca with radionuclide purity over 99.9%. The Z _PDGFRβ affibody was radiolabeled by ⁴⁷ Sc to obtain a ⁴⁷ Sc-DOTA-Z _PDGFRβ conjugate with radiochemical purity higher than 99%. Biodistribution studies showed that tumor uptake of ⁴⁷ Sc-DOTA-Z _PDGFRβ 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 ⁴⁷ Sc-DOTA-Z _PDGFRβ in PANC-2 pancreatic tumors. Therapeutic experiments revealed that ⁴⁷ Sc has an effective anti-tumor ability similar to ¹⁷⁷ Lu. Our research results indicated that the ⁴⁷ Sc-DOTA-Z _PDGFRβ conjugate exhibited remarkable targeting efficacy as a PDGFRβ-targeted radiotracer in SPECT imaging and also demonstrated favorable radiotherapy capabilities. SPECT imaging of ⁴⁷ Sc 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.