ArticleMolecular cancer therapeutics2012
Effects of anti-VEGF on pharmacokinetics, biodistribution, and tumor penetration of trastuzumab in a preclinical breast cancer model.
Article in Molecular cancer therapeutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 102 citations in OpenAlex.
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- Model-based prediction of effective target exposure for MEN1611 in combination with trastuzumab in HER2-positive advanced or metastatic breast cancer patients.CPT: pharmacometrics & systems pharmacology · 2023Article
- Tumor Response to Radiopharmaceutical Therapies: The Knowns and the Unknowns.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2021Review
- Strategies to enhance monoclonal antibody uptake and distribution in solid tumors.Cancer biology & medicine · 2021Review
- Antibody Format and Serum Disposition Govern Ocular Pharmacokinetics of Intravenously Administered Protein Therapeutics.Frontiers in pharmacology · 2021Article
- Understanding Inter-Individual Variability in Monoclonal Antibody Disposition.Antibodies (Basel, Switzerland) · 2019Review
- Biodistribution and efficacy of an anti-TENB2 antibody-drug conjugate in a patient-derived model of prostate cancer.Oncotarget · 2019Article
- How to schedule VEGF and PD-1 inhibitors in combination cancer therapy?BMC systems biology · 2019Article
- Review
- Tissue Physiology of Cynomolgus Monkeys: Cross-Species Comparison and Implications for Translational Pharmacology.The AAPS journal · 2018Article
- Heterogeneous distribution of trastuzumab in HER2-positive xenografts and metastases: role of the tumor microenvironment.Clinical & experimental metastasis · 2018Article
- Pharmacodynamic and Pharmacokinetic Markers For Anti-angiogenic Cancer Therapy: Implications for Dosing and Selection of Patients.European journal of drug metabolism and pharmacokinetics · 2018Review
- Pharmacokinetic Considerations for Antibody-Drug Conjugates against Cancer.Pharmaceutical research · 2017Review
- Review
- A novel individual-cell-based mathematical model based on multicellular tumour spheroids for evaluating doxorubicin-related delivery in avascular regions.British journal of pharmacology · 2017Article
- Linker stability influences the anti-tumor activity of acetazolamide-drug conjugates for the therapy of renal cell carcinoma.Journal of controlled release : official journal of the Controlled Release Society · 2017Article
- Harnessing Integrative Omics to Facilitate Molecular Imaging of the Human Epidermal Growth Factor Receptor Family for Precision Medicine.Theranostics · 2017Review
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Authors and funding
25 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Both human epidermal growth factor receptor 2 (HER-2/neu) and VEGF overexpression correlate with aggressive phenotypes and decreased survival among breast cancer patients. Concordantly, the combination of trastuzumab (anti-HER2) with bevacizumab (anti-VEGF) has shown promising results in preclinical xenograft studies and in clinical trials. However, despite the known antiangiogenic mechanism of anti-VEGF antibodies, relatively little is known about their effects on the pharmacokinetics and tissue distribution of other antibodies. This study aimed to measure the disposition properties, with a particular emphasis on tumor uptake, of trastuzumab in the presence or absence of anti-VEGF. Radiolabeled trastuzumab was administered alone or in combination with an anti-VEGF antibody to mice bearing HER2-expressing KPL-4 breast cancer xenografts. Biodistribution, autoradiography, and single-photon emission computed tomography-X-ray computed tomography imaging all showed that anti-VEGF administration reduced accumulation of trastuzumab in tumors despite comparable blood exposures and similar distributions in most other tissues. A similar trend was also observed for an isotype-matched IgG with no affinity for HER2, showing reduced vascular permeability to macromolecules. Reduced tumor blood flow (P < 0.05) was observed following anti-VEGF treatment, with no significant differences in the other physiologic parameters measured despite immunohistochemical evidence of reduced vascular density. In conclusion, anti-VEGF preadministration decreased tumor uptake of trastuzumab, and this phenomenon was mechanistically attributed to reduced vascular permeability and blood perfusion. These findings may ultimately help inform dosing strategies to achieve improved clinical outcomes.
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