Lymph node effective vascular permeability and chemotherapy uptake

作者：Meijer Eelco F J; Blatter Cedric; Chen Ivy X; Bouta Echoe; Jones Dennis; Pereira Ethel R; Jung Keehoon; Vakoc Benjamin J; Baish James W; Padera Timothy P

来源：Microcirculation, 2017, 24(6): e12381.

DOI：10.1111/micc.12381

• chemotherapy
• drug penetration
• intravital microscopy
• lymph node
• vascular permeability

ObjectiveLymph 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.
MethodsWe 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.
ResultsVEGF-A-treated lymph node blood vessel effective vascular permeability (mean 3.83 x 10(-7) cm/s) was significantly higher than untreated lymph nodes (mean 9.87 x 10(-8) cm/s). No difference was found in lymph node drug accumulation in untreated versus VEGF-A-treated mice.
ConclusionsLymph node effective vascular permeability can be increased (similar to fourfold) by VEGF-A. However, no significant increase in chemotherapy uptake was measured by pretreatment with VEGF-A.

• 出版日期2017-8