ArticlePloS one2017
Non invasive imaging assessment of the biodistribution of GSK2849330, an ADCC and CDC optimized anti HER3 mAb, and its role in tumor macrophage recruitment in human tumor-bearing mice.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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
20 citing papers in PubMed, 33 citations in OpenAlex.
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- Influence of Fc Modifications and IgG Subclass on Biodistribution of Humanized Antibodies Targeting L1CAM.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2022Article
- HER3 PET Imaging:Cancers · 2021Article
- Iron Oxide Nanoparticles as Theranostic Agents in Cancer Immunotherapy.Nanomaterials (Basel, Switzerland) · 2021Review
- Thirty Years of HER3: From Basic Biology to Therapeutic Interventions.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Review
- Novel Preclinical Patient-Derived Lung Cancer Models Reveal Inhibition of HER3 and MTOR Signaling as Therapeutic Strategies for NRG1 Fusion-Positive Cancers.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2021Article
- PET and SPECT Imaging of the EGFR Family (RTK Class I) in Oncology.International journal of molecular sciences · 2021Review
- The Radiolabeled HER3 Targeting Molecules for Tumor Imaging.Iranian journal of pharmaceutical research : IJPR · 2021Review
- Image-guided mathematical modeling for pharmacological evaluation of nanomaterials and monoclonal antibodies.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · 2020Review
- ImmunoPET: Concept, Design, and Applications.Chemical reviews · 2020Review
- Immuno-PET to Optimize the Dose of Monoclonal Antibodies for Cancer Therapy: How Much Is Enough?Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2019Article
- Prospects for pharmacological targeting of pseudokinases.Nature reviews. Drug discovery · 2019Review
- Immuno-PET Imaging to Assess Target Engagement: Experience fromJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2019Article
- Clinical Potential of Human Epidermal Growth Factor Receptor 2 and Human Epidermal Growth Factor Receptor 3 Imaging in Breast Cancer.PET clinics · 2018Review
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Corrections and comments
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The purpose of this work was to use various molecular imaging techniques to non-invasively assess GSK2849330 (anti HER3 ADCC and CDC enhanced 'AccretaMab' monoclonal antibody) pharmacokinetics and pharmacodynamics in human xenograft tumor-bearing mice. Immuno-PET biodistribution imaging of radiolabeled 89Zr-GSK2849330 was assessed in mice with HER3 negative (MIA-PaCa-2) and positive (CHL-1) human xenograft tumors. Dose dependency of GSK2849330 disposition was assessed using varying doses of unlabeled GSK2849330 co-injected with 89Zr-GSK2849330. In-vivo NIRF optical imaging and ex-vivo confocal microscopy were used to assess the biodistribution of GSK2849330 and the HER3 receptor occupancy in HER3 positive xenograft tumors (BxPC3, and CHL-1). Ferumoxytol (USPIO) contrast-enhanced MRI was used to investigate the effects of GSK2849330 on tumor macrophage content in CHL-1 xenograft bearing mice. Immuno-PET imaging was used to monitor the whole body drug biodistribution and CHL-1 xenograft tumor uptake up to 144 hours post injection of 89Zr-GSK2849330. Both hepatic and tumor uptake were dose dependent and saturable. The optical imaging data in the BxPC3 xenograft tumor confirmed the tumor dose response finding in the Immuno-PET study. Confocal microscopy showed a distinguished cytoplasmic punctate staining pattern within individual CHL-1 cells. GSK2849330 inhibited tumor growth and this was associated with a significant decrease in MRI signal to noise ratio after USPIO injection and with a significant increase in tumor macrophages as confirmed by a quantitative immunohistochemistry analysis. By providing both dose response and time course data from both 89Zr and fluorescently labeled GSK2849330, complementary imaging studies were used to characterize GSK2849330 biodistribution and tumor uptake in vivo. Ferumoxytol-enhanced MRI was used to monitor aspects of the immune system response to GSK2849330. Together these approaches potentially provide clinically translatable, non-invasive techniques to support dose optimization, and assess immune activation and anti-tumor responses.
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