ArticleCancer research2005
Optimizing radiolabeled engineered anti-p185HER2 antibody fragments for in vivo imaging.
Article in Cancer research, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed.
- GD2-Targeted Minibody-Drug Conjugates Match the Potency of IgG-Based ADCs in a Mouse Cancer Model.International journal of molecular sciences · 2026Article
- Preclinical Evaluation of an Anti-EphA2 Minibody-Based ImmunoPET Agent as a Diagnostic Tool For Cancer.Molecular imaging and biology · 2025Article
- Integrating Biochemical and Computational Approaches Reveal Structural Insights in Trastuzumab scFv-Fc Antibody Engineering.Biomolecules · 2025Article
- PET and SPECT Imaging of the EGFR Family (RTK Class I) in Oncology.International journal of molecular sciences · 2021Review
- Evaluation of HER2-specific peptide ligand for its employment as radiolabeled imaging probe.Scientific reports · 2018Article
- ImmunoPET Imaging of αMolecular imaging and biology · 2018Article
- Evaluation of antibody fragment properties for near-infrared fluorescence imaging of HER3-positive cancer xenografts.Theranostics · 2018Article
- Fluorine-18 Labeling of the HER2-Targeting Single-Domain Antibody 2Rs15d Using a Residualizing Label and Preclinical Evaluation.Molecular imaging and biology · 2017Article
- Molecular Simulation of Receptor Occupancy and Tumor Penetration of an Antibody and Smaller Scaffolds: Application to Molecular Imaging.Molecular imaging and biology · 2017Article
- Generation and evaluation of antibody agents for molecular imaging of CD44v6-expressing cancers.Oncotarget · 2017Article
- Gallium-68-labeled anti-HER2 single-chain Fv fragment: development and in vivo monitoring of HER2 expression.Molecular imaging and biology · 2015Article
- Improved tumor targeting of anti-HER2 nanobody through N-succinimidyl 4-guanidinomethyl-3-iodobenzoate radiolabeling.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2014Article
- Engineered antibody fragments for immuno-PET imaging of endogenous CD8+ T cells in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Pilot study of 68Ga-DOTA-F(ab')2-trastuzumab in patients with breast cancer.Nuclear medicine communications · 2013Article
- Antibody-based imaging of HER-2: moving into the clinic.Current molecular medicine · 2013Review
- Nanoparticles for combination drug therapy.ACS nano · 2013Article
- Advances in immuno-positron emission tomography: antibodies for molecular imaging in oncology.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2012Article
- Anti-carcinoembryonic antigen single-chain variable fragment antibody variants bind mouse and human neonatal Fc receptor with different affinities that reveal distinct cross-species differences in serum half-life.The Journal of biological chemistry · 2012Article
- An engineered cysteine-modified diabody for imaging activated leukocyte cell adhesion molecule (ALCAM)-positive tumors.Molecular imaging and biology · 2012Article
- In vivo Noninvasive Small Animal Molecular Imaging.Osong public health and research perspectives · 2012Review
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
We have recently described the in vivo properties of an iodinated anti-p185HER2 engineered antibody fragment [minibody (scFv-C(H)3)2; 80 kDa], made from the internalizing 10H8 monoclonal antibody. Although the 10H8 minibody showed excellent binding to the target in vitro, only modest tumor uptake [5.6 +/- 1.7% injected dose per gram (ID/g) of tissue] was achieved in nude mice bearing MCF7/HER2 breast cancer tumors. Here, in an attempt to improve targeting, the 10H8 minibody was conjugated to 1,4,7,10-tetraazacyclododecane-N, N', N'', N'''-tetraacetic acid (DOTA), radiometal labeled, and evaluated in vivo. The tumor uptake of 111In-DOTA 10H8 minibody was 5.7 +/- 0.1% ID/g, similar to the radioiodinated 10H8 minibody. However, in addition to the expected liver clearance, the kidneys had unexpectedly high activity (34.0 +/- 4.0% ID/g). A minibody derived from a second anti-p185(HER2) antibody (trastuzumab; hu4D5v8) was also made. Tumor uptakes, evaluated by quantitative microPET using 64Cu-DOTA hu4D5v8 minibody, were 4.2 +/- 0.5% ID/g. Furthermore, in non-tumor-bearing mice, 111In-DOTA hu4D5v8 minibody exhibited similar elevated uptake in the kidneys (28.4 +/- 6.5% ID/g). Immunohistochemical staining of kidneys from non-tumor-bearing mice showed strong specific staining of the proximal tubules, and Western blot analysis of kidney lysate confirmed the presence of cross-reactive antigen. To further improve tumor uptake and normal tissue distribution, a larger hu4D5v8 fragment [(scFv-C(H)2-C(H)3)2; 105 kDa] was made, engineered to exhibit rapid clearance kinetics. This fragment, when evaluated by microPET, exhibited improved tumor targeting (12.2 +/- 2.4% ID/g) and reduced kidney uptake (13.1 +/- 1.5% ID/g). Thus, by manipulating the size and format of anti-p185(HER2) antibody fragments, the kidney activity was reduced and high or low expression of p185HER2 in xenografts could be distinguished by microPET imaging.
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