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 (AVRTSAD) and developed three EDBp-based probes, Cy5-PEG4-EDBp(Cy5-EDBp), [F]-NOTA-PEG4-EDBp([F]-EDBp), and [Lu]-DOTA-PEG4-EDBp ([Lu]-EDBp), for 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, [F]-EDBp, and [Lu]-EDBp, were developed for fluorescence imaging, positron emission tomography (PET) imaging, and radiotherapy in TC tumor-bearing mice, respectively. Additionally, [F]-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. [F]-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 [Lu]-EDBp inhibited tumor growth and prolonged survival in TC tumor-bearing mice (survival time of different treatment groups: saline vs. EDBp vs. ABRAXANE vs. [Lu]-EDBp = 8.00 d vs. 8.00 d vs. 11.67 d vs. 22.33 d, ***p < 0.001). Importantly, the first-in-human evaluation of [F]-EDBp demonstrated that it had specific targeting properties (SUVmax value of 3.6) and safety.
Conclusion: Cy5-EDBp, [F]-EDBp, and [Lu]-EDBp are promising candidates for the surgical navigation, radionuclide imaging, and radionuclide therapy of TC, respectively.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s00259-023-06147-x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
EDB-FN-targeted probes for near infrared fluorescent imaging and positron emission tomography imaging of breast cancer in mice.
Sci Rep
September 2024
School of Nursing, Guangdong Pharmaceutical University, 280 East Waihuan Road, Guangzhou, 510006, China.
The extra domain B splice variant of fibronectin (EDB-FN), which is overexpressed in several cancers, is an approved diagnostic and therapeutic target of cancers. The aim of this study was to evaluate the EDB-FN-targeting peptide EDBp as a noninvasive imaging modality for molecular imaging of breast cancer in mice. Western blot, flow cytometry and immunofluorescence were used to assess the expression level of EDB-FN and its binding to EDRp in MCF7, SKBR3, 4T1, EMT6, MDA-MB-231 and MDA-MB-453 cells.
View Article and Find Full Text PDFMR Molecular Imaging of Extradomain-B Fibronectin for Assessing Progression and Therapy Resistance of Prostate Cancer.
Chem Biomed Imaging
August 2024
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, United States.
Accurate assessment and characterization of the progression and therapy response of prostate cancer are essential for precision healthcare of patients diagnosed with the disease. MRI is a clinical imaging modality routinely used for diagnostic imaging and treatment planning of prostate cancer. Extradomain B fibronectin (EDB-FN) is an oncofetal subtype of fibronectin highly expressed in the extracellular matrix of aggressive cancers, including prostate cancer.
View Article and Find Full Text PDFMR Molecular Image Guided Treatment of Pancreatic Cancer with Targeted ECO/miR-200c Nanoparticles in Immunocompetent Mouse Tumor Models.
Pharm Res
September 2024
Department of Biomedical Engineering, Case Western Reserve University, Wickenden 427, 10900 Euclid Avenue, Cleveland, OH, 44106, USA.
Article Synopsis
- The study explores the use of targeted nanoparticles (RGD-ELNP) carrying miR-200c to modify the extracellular matrix (ECM) in pancreatic ductal adenocarcinoma (PDAC) and inhibit tumor growth.
- In mouse models, the treatment significantly reduced ECM proteins associated with tumor progression and inhibited the ability of PDAC cells to form structures and migrate.
- Non-invasive imaging techniques (MT218-MRMI) effectively tracked changes in tumor ECM and confirmed the therapeutic efficacy of RGD-ELNP/miR-200c, showing promise for improving PDAC treatment strategies.
Assessment of the Efficacy of the Combination of RNAi of lncRNA DANCR with Chemotherapy to Treat Triple Negative Breast Cancer Using Magnetic Resonance Molecular Imaging.
Bioconjug Chem
March 2024
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, United States.
Long noncoding RNA (lncRNA) differentiation antagonizing noncoding RNA (DANCR) is overexpressed in human triple-negative breast cancer (TNBC) and promotes cell migration and proliferation. TNBC is limited in treatment options relative to hormone-receptor-positive breast cancer and is commonly treated with chemotherapy, which is often compromised by acquired resistance. DANCR has been implicated in the development of chemoresistance across multiple cancer types.
View Article and Find Full Text PDFMagnetic-optical dual-modality imaging monitoring chemotherapy efficacy of pancreatic ductal adenocarcinoma with a low-dose fibronectin-targeting Gd-based contrast agent.
Eur J Nucl Med Mol Imaging
June 2024
Department of Radiology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Beijing, 100730, China.
Purpose: Pancreatic ductal adenocarcinoma (PDAC) is a lethal hypovascular tumor surrounded by dense fibrosis. Albumin-bound paclitaxel and gemcitabine (AG) chemotherapy is the mainstay of PDAC treatment through depleting peritumoral fibrosis and killing tumor cells; however, it remains challenging due to the lack of a noninvasive imaging method evaluating fibrotic changes during AG chemotherapy. In this study, we developed a dual-modality imaging platform that enables noninvasive, dynamic, and quantitative assessment of chemotherapy-induced fibrotic changes through near-infrared fluorescence molecular imaging (FMI) and magnetic resonance imaging (MRI) using an extradomain B fibronectin (EDB-FN)-targeted imaging probe (ZD2-Gd-DOTA-Cy7).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!