EDB-FN targeted probes for the surgical navigation, radionuclide imaging and therapy of thyroid cancer

Abstract Purpose Extradomain B of fibronectin (EDB-FN) is a promising diagnostic and therapeutic biomarker for thyroid cancer (TC). Here, we identified a high-affinity EDB-FN targeted peptide named EDBp, and developed three EDBp-based probes, Cy5-EDBp, [18F]-EDBp and [177Lu]-EDBp the surgical navigation, radionuclide imaging and therapy of TC. Methods Based on the previously identified EDB-FN targeted peptide ZD2, the optimized EDB-FN targeted peptide EDBp was identified by using the alanine scan strategy. Three EDBp-based probes, Cy5-EDBp, [18F]-EDBp and [177Lu]-EDBp, were developed for fluorescence imaging, positron emission tomography (PET) imaging and radiotherapy in TC tumor-bearing mice, respectively. Additionally, [18F]-EDBp was evaluated in two TC patients. Results The binding affinity of EDBp to the EDB fragment protein (Kd = 14.4 ± 1.4 nM, n = 3) was approximately 336-fold greater than that of the ZD2 (Kd = 4839.7 ± 361.7 nM, n = 3). Fluorescence imaging with Cy5-EDBp facilitated the complete removal of TC tumors. [18F]-EDBp PET imaging clearly delineated TC tumors, with high tumor uptake (16.43 ± 1.008%ID/g, n = 6, at 1 h postinjection). Radiotherapy with [177Lu]-EDBp inhibited tumor growth and prolonged survival in TC tumor-bearing mice (survival time of different treatment groups: Saline vs. EDBp vs. ABRAXANE vs. [177Lu]-EDBp = 8 d vs. 8 d vs. 11.67 d vs. 22.33 d, ***p < 0.001). Importantly, the first-in-human evaluation of [18F]-EDBp demonstrated that it had specific targeting properties (SUVmax value of 3.6) and safety. Conclusion Cy5-EDBp, [18F]-EDBp and [177Lu]-EDBp are promising candidates for the surgical navigation, radionuclide imaging and radionuclide therapy of TC, respectively.