Evidence map›Paper›PMID 39600235›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025

Fluorescence Lifetime Imaging for Quantification of Targeted Drug Delivery in Varying Tumor Microenvironments.

Amit Verma, Vikas Pandey, Catherine Sherry, Taylor Humphrey, Christopher James, Kailie Matteson, Jason T Smith, Alena Rudkouskaya, Xavier Intes, Margarida Barroso

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Journal of pharmaceutical analysis · 2025
    Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. AlliGator: Open Source Fluorescence Lifetime Imaging Analysis in G.bioRxiv : the preprint server for biology · 2025
    Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Amit VermaDepartment of Molecular and Cellular Physiology, Albany Medical College, Albany, NY, 12208, USA.
Vikas PandeyDepartment of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA.
Catherine SherryDepartment of Molecular and Cellular Physiology, Albany Medical College, Albany, NY, 12208, USA.
Taylor HumphreyDepartment of Molecular and Cellular Physiology, Albany Medical College, Albany, NY, 12208, USA.
Christopher JamesDepartment of Molecular and Cellular Physiology, Albany Medical College, Albany, NY, 12208, USA.
Kailie MattesonDepartment of Molecular and Cellular Physiology, Albany Medical College, Albany, NY, 12208, USA.
Jason T SmithDepartment of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA.
Alena RudkouskayaDepartment of Molecular and Cellular Physiology, Albany Medical College, Albany, NY, 12208, USA.
Xavier IntesDepartment of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA.ORCID 0000-0001-5868-4845
Margarida BarrosoDepartment of Molecular and Cellular Physiology, Albany Medical College, Albany, NY, 12208, USA.ORCID 0000-0002-0407-3181

Funding

Role of tumor heterogeneity on receptor engagementR01CA207725 · NCI · RENSSELAER POLYTECHNIC INSTITUTE · PI BARROSO, MARGARIDA, CORR, DAVID THOMAS · 2017 to 2021
$3.0M
In vivo Macroscopic Fluorescence Lifetime Molecular Optical ImagingR01CA250636 · NCI · RENSSELAER POLYTECHNIC INSTITUTE · PI BARROSO, MARGARIDA, INTES, XAVIER · 2020 to 2023
$2.9M
Photon-counting X-ray and Optical Tomography for Preclinical Cancer ResearchR01CA237267 · NCI · RENSSELAER POLYTECHNIC INSTITUTE · PI BARROSO, MARGARIDA, INTES, XAVIER · 2019 to 2023
$2.9M
AI enhanced lifetime-based mesoscopic in vivo imaging of tissue molecular heterogeneityR01CA271371 · NCI · RENSSELAER POLYTECHNIC INSTITUTE · PI Margarida Barroso, Xavier Intes · 2023 to 2026
$2.7M
NCI NIH HHS R01 CA207725NCI NIH HHS R01 CA237267NCI NIH HHS R01 CA250636NCI NIH HHS R01 CA271371NIH HHS R01 CA207725NIH HHS R01 CA237267NIH HHS R01 CA250636NIH HHS R01 CA271371
6 · The paper itself

Abstract

Trastuzumab (TZM) is a monoclonal antibody that targets the human epidermal growth factor receptor 2 (HER2) and is clinically used for the treatment of HER2-positive breast tumors. However, the tumor microenvironment can limit the access of TZM to the HER2 targets across the whole tumor and thereby compromising TZM's therapeutic efficacy. An imaging methodology that can non-invasively quantify the binding of TZM-HER2, which is required for therapeutic action, and distribution within tumors with varying tumor microenvironments is much needed. Near-infrared (NIR) fluorescence lifetime (FLI) Forster Resonance Energy Transfer (FRET) is performed to measure TZM-HER2 binding, using in vitro microscopy and in vivo widefield macroscopy, in HER2 overexpressing breast and ovarian cancer cells and tumor xenografts, respectively. Immunohistochemistry is used to validate in vivo imaging results. NIR FLI FRET in vitro microscopy data show variations in intracellular distribution of bound TZM in HER2-positive breast AU565 and AU565 tumor-passaged XTM cell lines in comparison to SKOV-3 ovarian cancer cells. Macroscopy FLI (MFLI) FRET in vivo imaging data show that SKOV-3 tumors display reduced TZM binding compared to AU565 and XTM tumors, as validated by ex vivo immunohistochemistry. Moreover, AU565/XTM and SKOV-3 tumor xenografts display different amounts and distributions of TME components, such as collagen and vascularity. Therefore, these results suggest that SKOV-3 tumors are refractory to TZM delivery due to their disrupted vasculature and increased collagen content. The study demonstrates that FLI is a powerful analytical tool to monitor the delivery of antibodydrugs both in cell cultures and in vivo live systems. Especially, MFLI FRET is a unique imaging modality that can directly quantify target engagement with the potential to elucidate the role of the TME in drug delivery efficacy in intact live tumor xenografts.

Indexed as

Breast NeoplasmsDrug Delivery SystemsOptical ImagingOvarian NeoplasmsTrastuzumabTumor MicroenvironmentAnimalsCell Line, TumorErb-b2 Receptor Tyrosine KinasesFemaleFluorescence Resonance Energy TransferHumansMiceMice, NudeXenograft Model Antitumor AssaysERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesTrastuzumabbreast tumorfluorescence lifetime imagingFRETHER2targeted drug deliverytarget engagementTrastuzumabtumor microenvironment

Identifiers

PMID39600235
PMCPMC11744649

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Registered trials

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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.