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Unlabelled: The overexpression and excessive signaling of platelet-derived growth factor receptor β (PDGFRβ) has been detected in cancers, atherosclerosis, and a variety of fibrotic diseases. Radionuclide in vivo visualization of PDGFRβ expression might help to select PDGFRβ targeting treatment for these diseases. The goal of this study was to evaluate the feasibility of in vivo radionuclide imaging of PDGFRβ expression using an Affibody molecule, a small nonimmunoglobulin affinity protein.
Methods: The PDGFRβ-binding Z09591 Affibody molecule was site-specifically conjugated with a maleimido derivative of DOTA and labeled with (111)In. Targeting of the PDGFRβ-expressing U-87 MG glioblastoma cell line using (111)In-DOTA-Z09591 was evaluated in vitro and in vivo.
Results: DOTA-Z09591 was stably labeled with (111)In with preserved specific binding to PDGFRβ-expressing cells in vitro. The dissociation constant for (111)In-DOTA-Z09591 binding to U-87 MG cells was determined to be 92 ± 10 pM. In mice bearing U-87 MG xenografts, the tumor uptake of (111)In-DOTA-Z09591 was 7.2 ± 2.4 percentage injected dose per gram and the tumor-to-blood ratio was 28 ± 14 at 2 h after injection. In vivo receptor saturation experiments demonstrated that targeting of U-87 MG xenografts in mice was PDGFRβ-specific. U-87 MG xenografts were clearly visualized using small-animal SPECT/CT at 3 h after injection.
Conclusion: This study demonstrates the feasibility of in vivo visualization of PDGFRβ-expressing xenografts using an Affibody molecule. Further development of radiolabeled Affibody molecules might provide a useful clinical imaging tool for PDGFRβ expression during various pathologic conditions.
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http://dx.doi.org/10.2967/jnumed.113.121814 | DOI Listing |
Mol Pharm
December 2024
Department of Biomedical Engineering, University of Minnesota-Twin Cities, Minneapolis, Minnesota 55455, United States.
Selective delivery of therapeutic modalities to tumor cells via binding of tumor-selective cell-surface biomarkers has empowered substantial advances in cancer treatment. Yet, tumor cells generally lack a truly specific biomarker that is present in high density on tumor tissue while being completely absent from healthy tissue. Rather, low but nonzero expression in healthy tissues results in on-target, off-tumor activity with detrimental side effects that constrain the therapeutic window or prevent use altogether.
View Article and Find Full Text PDFMol Cancer Ther
December 2024
Dartmouth-Hitchcock Medical Center, Lebanon, NH, United States.
ABY-029, an anti-epidermal growth factor receptor (EGFR) Affibody® molecule conjugated to IRDye 800CW, recently underwent first-in-human testing in soft-tissue sarcoma (STS). FDA Exploratory Investigational New Drug status was obtained for the Phase 0 clinical trial in which study objectives were to determine whether biological variance ratio (BVR) of 10 was achievable, fluorescence intensity correlated with EGFR expression, and doses were well tolerated. Patients (N=12) with STS were recruited based on positive EGFR immunohistochemical staining of diagnostic biopsies.
View Article and Find Full Text PDFGastric Cancer
December 2024
Institute of Molecular Virology and Immunology, Department of Microbiology and Immunology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, People's Republic of China.
Gastric cancer (GC) has a poor prognosis and high mortality because it is often diagnosed at an advanced stage. Targeted therapeutics are considered an important class for advanced GC treatment. However, the fewer effective therapeutic targets and the poor coverage of the GC population limit the use of GC targeted therapies.
View Article and Find Full Text PDFClin Nucl Med
January 2025
From the Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Beijing, China.
Purpose: Accuracy in in vivo assessment of human epidermal growth factor receptor type 2 (HER2) status is crucial for predicting the response to HER2-targeted therapies in breast cancer. This study assessed the safety, feasibility, and diagnostic accuracy of 99mTc-ABH2, a reengineered affibody molecule with radionuclide labeling, for HER2 expression in breast cancer using SPECT/CT imaging, compared with 18F-FDG PET/CT.
Patients And Methods: Thirty-six patients suspected of primary breast cancer were enrolled in this prospective, single-center study from March to July in 2023.
Cells
November 2024
Institute of Molecular Virology and Immunology, Department of Microbiology and Immunology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, China.
Nasopharyngeal carcinoma (NPC) is a tumor of the head and neck, with a higher incidence in southern China and Southeast Asia. Radiotherapy and chemotherapy are the main treatments; however, metastasis and recurrence remain the main causes of treatment failure. Further, the majority of patients are diagnosed in the late stage due to lack of tumor-specific biomarker for early diagnosis.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!