ArticleProceedings of the National Academy of Sciences of the United States of America2015
Noninvasive brain cancer imaging with a bispecific antibody fragment, generated via click chemistry.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
45 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Glioblastoma multiforme (GBM): An overview of current therapies and mechanisms of resistance.Pharmacological research · 2021Pooled it
- Endoglin/CD105-Based Imaging of Cancer and Cardiovascular Diseases: A Systematic Review.International journal of molecular sciences · 2021Pooled it
- Article
- Phage-Selected Clickable Gln-Donor Peptide for Lys-Selective Fab Labeling Using Engineered Microbial Transglutaminase.Antibodies (Basel, Switzerland) · 2026Article
- Bispecific brain-penetrant antibodies for treatment of Alzheimer's disease.The journal of prevention of Alzheimer's disease · 2025Review
- Advances in immunoPET/SPECT imaging: The role of Fab and F(ab')Acta pharmaceutica Sinica. B · 2025Review
- The fibronectin-targeting PEG-FUD imaging probe shows enhanced uptake during fibrogenesis in experimental lung fibrosis.Respiratory research · 2025Article
- Discovery of a highly specific radiolabeled antibody targeting B-cell maturation antigen: Applications in PET imaging of multiple myeloma.European journal of nuclear medicine and molecular imaging · 2025Article
- Molecular imaging supports the development of multispecific cancer antibodies.Nature reviews. Clinical oncology · 2024Review
- Engineered Antibodies as Cancer Radiotheranostics.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- A bibliometric and knowledge-map analysis of bispecific antibodies in cancer immunotherapy from 2000 to 2023.Heliyon · 2024Article
- Glioma stem cells remodel immunotolerant microenvironment in GBM and are associated with therapeutic advancements.Cancer biomarkers : section A of Disease markers · 2024Review
- Crosstalk with lung fibroblasts shapes the growth and therapeutic response of mesothelioma cells.Cell death & disease · 2023Article
- ImmunoPET Directed to the Brain: A New Tool for Preclinical and Clinical Neuroscience.Biomolecules · 2023Review
- Hetero-bivalent agents targeting FAP and PSMA.European journal of nuclear medicine and molecular imaging · 2022Article
- Enhancing fibroblast activation protein (FAP)-targeted radionuclide therapy with albumin binding, and beyond.European journal of nuclear medicine and molecular imaging · 2022Article
- Article
- Laser capture microdissection-capillary zone electrophoresis-tandem mass spectrometry (LCM-CZE-MS/MS) for spatially resolved top-down proteomics: a pilot study of zebrafish brain.Molecular omics · 2022Article
- Immunotherapy for glioblastoma: the promise of combination strategies.Journal of experimental & clinical cancer research : CR · 2022Review
- ImmunoPET: Antibody-Based PET Imaging in Solid Tumors.Frontiers in medicine · 2022Review
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Early diagnosis remains a task of upmost importance for reducing cancer morbidity and mortality. Successful development of highly specific companion diagnostics targeting aberrant molecular pathways of cancer is needed for sensitive detection, accurate diagnosis, and opportune therapeutic intervention. Herein, we generated a bispecific immunoconjugate [denoted as Bs-F(ab)2] by linking two antibody Fab fragments, an anti-epidermal growth factor receptor (EGFR) Fab and an anti-CD105 Fab, via bioorthogonal "click" ligation of trans-cyclooctene and tetrazine. PET imaging of mice bearing U87MG (EGFR/CD105(+/+)) tumors with (64)Cu-labeled Bs-F(ab)2 revealed a significantly enhanced tumor uptake [42.9 ± 9.5 percentage injected dose per gram (%ID/g); n = 4] and tumor-to-background ratio (tumor/muscle ratio of 120.2 ± 44.4 at 36 h postinjection; n = 4) compared with each monospecific Fab tracer. Thus, we demonstrated that dual targeting of EGFR and CD105 provides a synergistic improvement on both affinity and specificity of (64)Cu-NOTA-Bs-F(ab)2. (64)Cu-NOTA-Bs-F(ab)2 was able to visualize small U87MG tumor nodules (<5 mm in diameter), owing to high tumor uptake (31.4 ± 10.8%ID/g at 36 h postinjection) and a tumor/muscle ratio of 76.4 ± 52.3, which provided excellent sensitivity for early detection. Finally, we successfully confirmed the feasibility of a ZW800-1-labeled Bs-F(ab)2 for near-infrared fluorescence imaging and image-guided surgical resection of U87MG tumors. More importantly, our rationale can be used in the construction of other disease-targeting bispecific antibody fragments for early detection and diagnosis of small malignant lesions.
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