Lymph Node Effective Vascular Permeability and Chemotherapy Uptake

Authors

Eelco F. J. Meijer, Massachusetts General Hospital and Harvard Medical School
Cedric Blatter, Harvard Medical School
Ivy X. Chen, Massachusetts General Hospital and Harvard Medical School
Echoe Bouta, Massachusetts General Hospital and Harvard Medical School
Dennis Jones, Massachusetts General Hospital and Harvard Medical SchoolFollow
Ethel R. Pereira, Massachusetts General Hospital and Harvard Medical SchoolFollow
Keehoon Jung, Massachusetts General Hospital and Harvard Medical SchoolFollow
Benjamin J. Vakoc, Massachusetts General Hospital and Harvard Medical School
James W. Baish, Bucknell UniversityFollow
Timothy P. Padera, Massachusetts General Hospital and Harvard Medical SchoolFollow

Publication Date

8-3-2017

Description

Objective

Lymph node metastases are a poor prognostic factor. Additionally, responses of lymph node metastasis to therapy can be different from the primary tumor. Investigating the physiologic lymph node blood vasculature might give insight into the ability of systemic drugs to penetrate the lymph node, and thus into the differential effect of therapy between lymph node metastasis and primary tumors. Here, we measured effective vascular permeability of lymph node blood vessels and attempted to increase chemotherapy penetration by increasing effective vascular permeability.

Methods

We developed a novel three-dimensional method to measure effective vascular permeability in murine lymph nodes in vivo. VEGF-A was systemically administered to increase effective vascular permeability. Validated high-performance liquid chromatography protocols were used to measure chemotherapeutic drug concentrations in untreated and VEGF-A-treated lymph nodes, liver, spleen, brain, and blood.

Results

VEGF-A-treated lymph node blood vessel effective vascular permeability (mean 3.83 × 10⁻⁷ cm/s) was significantly higher than untreated lymph nodes (mean 9.87 × 10⁻⁸ cm/s). No difference was found in lymph node drug accumulation in untreated versus VEGF-A-treated mice.

Conclusions

Lymph node effective vascular permeability can be increased (~fourfold) by VEGF-A. However, no significant increase in chemotherapy uptake was measured by pretreatment with VEGF-A.

Journal

Microcirculation

Volume

24

Issue

6

First Page

e12381

Department

Biomedical Engineering

Link to Published Version

https://doi.org/10.1111/micc.12381

DOI

10.1111/micc.12381

Recommended Citation

Meijer, Eelco F. J.; Blatter, Cedric; Chen, Ivy X.; Bouta, Echoe; Jones, Dennis; Pereira, Ethel R.; Jung, Keehoon; Vakoc, Benjamin J.; Baish, James W.; and Padera, Timothy P.. "Lymph Node Effective Vascular Permeability and Chemotherapy Uptake." Microcirculation (2017) : e12381.