ArticleJournal of pharmaceutical sciences2014
Multichannel imaging to quantify four classes of pharmacokinetic distribution in tumors.
Article in Journal of pharmaceutical sciences, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
19 citing papers in PubMed.
- Agent-based modeling demonstrates how target-independent processes supplement killing by antibody-drug conjugates in cancer therapy.PLoS computational biology · 2026Article
- Imaging Cell Surface Plectin in PDAC Patients - A First-In-Human Phase 0 Study Report.Molecular imaging and biology · 2025Article
- Clinical translation of antibody drug conjugate dosing in solid tumors from preclinical mouse data.Science advances · 2024Review
- Mechanistically Weighted Metric to Predict In Vivo Antibody-Receptor Occupancy: An Analytical Approach.The Journal of pharmacology and experimental therapeutics · 2023Article
- Imaging the Alternatively Spliced D Domain of Tenascin C in a Preclinical Model of Inflammatory Bowel Disease.Molecular imaging and biology · 2023Article
- Design of high avidity and low affinity antibodies for in situ control of antibody drug conjugate targeting.Scientific reports · 2022Article
- Cellular-Resolution Imaging of Bystander Payload Tissue Penetration from Antibody-Drug Conjugates.Molecular cancer therapeutics · 2022Article
- Antibody Co-Administration Can Improve Systemic and Local Distribution of Antibody-Drug Conjugates to IncreaseMolecular cancer therapeutics · 2021Article
- Increased Tumor Penetration of Single-Domain Antibody-Drug Conjugates ImprovesCancer research · 2020Article
- An Agent-Based Systems Pharmacology Model of the Antibody-Drug Conjugate Kadcyla to Predict Efficacy of Different Dosing Regimens.The AAPS journal · 2020Article
- Hitting Undruggable Targets: Viewing Stabilized Peptide Development through the Lens of Quantitative Systems Pharmacology.Trends in biochemical sciences · 2019Review
- Improved Tumor Penetration and Single-Cell Targeting of Antibody-Drug Conjugates Increases Anticancer Efficacy and Host Survival.Cancer research · 2018Article
- Imaging of anticancer drug action in single cells.Nature reviews. Cancer · 2017Review
- Importance of Drug Pharmacokinetics at the Site of Action.Clinical and translational science · 2017Review
- Tracking Antibody Distribution with Near-Infrared Fluorescent Dyes: Impact of Dye Structure and Degree of Labeling on Plasma Clearance.Molecular pharmaceutics · 2017Article
- Multiscale Modeling of Antibody-Drug Conjugates: Connecting Tissue and Cellular Distribution to Whole Animal Pharmacokinetics and Potential Implications for Efficacy.The AAPS journal · 2016Article
- Mechanistic and quantitative insight into cell surface targeted molecular imaging agent design.Scientific reports · 2016Article
- Quantitative Impact of Plasma Clearance and Down-regulation on GLP-1 Receptor Molecular Imaging.Molecular imaging and biology · 2016Article
- Residualization Rates of Near-Infrared Dyes for the Rational Design of Molecular Imaging Agents.Molecular imaging and biology · 2015Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Low and heterogeneous delivery of drugs and imaging agents to tumors results in decreased efficacy and poor imaging results. Systemic delivery involves a complex interplay of drug properties and physiological factors, and heterogeneity in the tumor microenvironment makes predicting and overcoming these limitations exceptionally difficult. Theoretical models have indicated that there are four different classes of pharmacokinetic behavior in tissue, depending on the fundamental steps in distribution. In order to study these limiting behaviors, we used multichannel fluorescence microscopy and stitching of high-resolution images to examine the distribution of four agents in the same tumor microenvironment. A validated generic partial differential equation model with a graphical user interface was used to select fluorescent agents exhibiting these four classes of behavior, and the imaging results agreed with predictions. BODIPY-FL exhibited higher concentrations in tissue with high blood flow, cetuximab gave perivascular distribution limited by permeability, high plasma protein and target binding resulted in diffusion-limited distribution for Hoechst 33342, and Integrisense 680 was limited by the number of binding sites in the tissue. Together, the probes and simulations can be used to investigate distribution in other tumor models, predict tumor drug distribution profiles, and design and interpret in vivo experiments.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.