Investigation of a Sc-radiolabelled PDGFRβ-targeted affibody in SPECT imaging and radiotherapy for pancreatic cancer.

[UNLABELLED] Pancreatic cancer is a malignant solid tumour that contains a large number of cancer-associated fibroblasts (CAFs). Therefore, evaluating tumour disease progression and planning radionuclide therapy using molecular imaging of CAF biomarkers are crucial. Platelet-derived growth factor receptor β (PDGFRβ) is highly expressed in fibroblasts, and a specific affinity probe, Z that binds to PDGFRβ was successfully developed. In this study, Sc was used to label the affibody targeting PDGFRβ to explore its distribution characteristics in pancreatic cancer and the therapeutic effect of radionuclides. Sc was produced using thermal neutron irradiation-enriched Ca with a radionuclide purity greater than 99.9%. The Z affibody was radiolabelled with Sc to obtain a Sc-DOTA-Z conjugate with a radiochemical purity greater than 99%. Biodistribution studies revealed that tumour uptake of Sc-DOTA-Z reached 4.57 ± 2.12% ID/g at 1 h postinjection and 4.00 ± 0.71% ID/g at 96 h postinjection. However, the uptake by the liver and kidneys reached 10.44 ± 3.19% ID/g and 49.90 ± 8.89% ID/g, respectively, at 1 h postinjection. Then, the uptake was reduced to 2.20 ± 1.04% ID/g and 2.60 ± 0.27% ID/g at 96 h postinjection. Single-photon emission computed tomography (SPECT) imaging indicated specific uptake of Sc-DOTA-Z in PANC-2 pancreatic tumours. Similar to 177Lu, Sc exhibits an effective antitumour ability. Our results indicated that the Sc-DOTA-Z conjugate exhibited remarkable targeting efficacy as a PDGFRβ-targeted radiotracer in SPECT imaging and demonstrated favourable radiotherapy capabilities. SPECT imaging of Sc ions also revealed characteristic distribution patterns in the cardiac, aortic, and hepatic regions, which has significant implications for future pharmaceutical development and radiation side effect prediction.

[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1186/s12885-025-15506-w.