Academic Journal
Preclinical evaluation of the antibody fragment targeting fibronectin EDB in the theranostics of radioactive iodine-resistant thyroid cancer.
| Τίτλος: | Preclinical evaluation of the antibody fragment targeting fibronectin EDB in the theranostics of radioactive iodine-resistant thyroid cancer. |
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| Συγγραφείς: | Luo W; Department of Nuclear Medicine, The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, No. 4, Fourth Section, North Ring Road, Chenghua District, Chengdu 610051, Sichuan, China., Zhang X; Department of Nuclear Medicine, The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, No. 4, Fourth Section, North Ring Road, Chenghua District, Chengdu 610051, Sichuan, China., Liu Q; Department of Nuclear Medicine, The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, No. 4, Fourth Section, North Ring Road, Chenghua District, Chengdu 610051, Sichuan, China., Shi Y; Department of Nuclear Medicine, The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, No. 4, Fourth Section, North Ring Road, Chenghua District, Chengdu 610051, Sichuan, China. Electronic address: shiyuhong89@126.com., Jiang X; Department of Nuclear Medicine, The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, No. 4, Fourth Section, North Ring Road, Chenghua District, Chengdu 610051, Sichuan, China. Electronic address: jiangxue1986Hh@163.com. |
| Πηγή: | Bioorganic chemistry [Bioorg Chem] 2026 Aug 15; Vol. 178, pp. 109980. Date of Electronic Publication: 2026 May 10. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Country of Publication: United States NLM ID: 1303703 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2120 (Electronic) Linking ISSN: 00452068 NLM ISO Abbreviation: Bioorg Chem Subsets: MEDLINE |
| Imprint Name(s): | Publication: Amsterdam : Elsevier Original Publication: New York, London, Academic Press. |
| Ιατρικοί όροι (MeSH): | Thyroid Neoplasms*/drug therapy , Thyroid Neoplasms*/diagnostic imaging , Thyroid Neoplasms*/metabolism , Thyroid Neoplasms*/radiotherapy , Thyroid Neoplasms*/pathology , Fibronectins*/antagonists & inhibitors , Fibronectins*/immunology , Fibronectins*/metabolism , Antineoplastic Agents*/pharmacology , Antineoplastic Agents*/chemistry , Antineoplastic Agents*/chemical synthesis , Immunoglobulin Fragments*/chemistry , Immunoglobulin Fragments*/pharmacology , Radiopharmaceuticals*/chemistry , Radiopharmaceuticals*/pharmacology , Theranostic Nanomedicine*, Lutetium/chemistry ; Zirconium/chemistry ; Cell Proliferation/drug effects ; Radioisotopes/chemistry ; Humans ; Animals ; Mice ; Iodine Radioisotopes ; Tissue Distribution ; Mice, Nude ; Drug Screening Assays, Antitumor ; Mice, Inbred BALB C ; Drug Evaluation, Preclinical ; Dose-Response Relationship, Drug ; Molecular Structure ; Structure-Activity Relationship ; Cell Line, Tumor |
| Περίληψη: | Objective: Radioactive iodine-resistant thyroid cancer (RAIR-TC) poses diagnostic and therapeutic challenges due to the absence of sodium/iodide symporter (NIS) expression. This study aims to evaluate the preclinical value of 89Zr-DFO-EDB and 177Lu-DTPA-EDB, an antibody fragment targeting fibronectin EDB (FN-EDB), in the theranostics of RAIR-TC. Methods: A CAL-62 human iodine-resistant thyroid cancer xenograft mouse model was established. The EDB antibody fragment (approximately 100 kD), selected through phage display technology, was labeled with 89Zr and 177Lu, respectively. The targeting characteristics of 89Zr-DFO-EDB and 177Lu-DTPA-EDB in the CAL-62 and NIS-silenced models were analyzed using dynamic micro-PET/CT imaging and ex vivo biodistribution. The anti-tumor efficacy and safety were assessed by a single treatment with 100 μCi of 177Lu-DTPA-EDB. Results: The labeling efficiency of 89Zr-DFO-EDB was 90.9%, with a radiochemical purity (RCP) of >99% and stability >98% at 180 min. Imaging showed that tumor uptake peaked at 72 h (13.8 ± 3.32%ID/g) and the liver was the main metabolic organ. High tumor uptake (16.1 ± 1.85%ID/g) was observed in the NIS-silenced model, confirming that EDB antibody targeting is independent of NIS status. The labeling efficiency of 177Lu-DTPA-EDB was 87.7%, with an RCP of >98.6% and stability >95% at 48 h. In the treatment group, tumor volume decreased by 78.5%, with a relative proliferation rate T/C of 25.05% (<40%). Pathological examination revealed necrosis areas >65%, with only transient weight loss (5.2%) and mild hepatocyte degeneration observed. Conclusion: 89Zr-DFO-EDB and 177Lu-DTPA-EDB achieved precise theranostics of RAIR-TC by targeting EDB-FN, with excellent imaging contrast and significant therapeutic effects, providing an innovative strategy for clinical translation in NIS-negative thyroid cancer. (Copyright © 2026. Published by Elsevier Inc.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: (177)Lu; (89)Zr; FN-EDB; Iodine-resistant thyroid cancer; Radioactive ligand therapy; Theranostics |
| Substance Nomenclature: | 0 (Fibronectins) 0 (Iodine Radioisotopes) 5H0DOZ21UJ (Lutetium) 0 (Antineoplastic Agents) 0 (Immunoglobulin Fragments) C6V6S92N3C (Zirconium) 0 (Radiopharmaceuticals) 0 (Radioisotopes) |
| Entry Date(s): | Date Created: 20260512 Date Completed: 20260716 Latest Revision: 20260716 |
| Update Code: | 20260717 |
| DOI: | 10.1016/j.bioorg.2026.109980 |
| PMID: | 42119207 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1090-2120 |
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| DOI: | 10.1016/j.bioorg.2026.109980 |