Macromolecule extravasation-xenograft size matters: a systematic study using probe-based confocal laser endomicroscopy (pCLE).

ABSTRACT:

Purpose

Profound changes of the vasculature in tumors critically impact drug delivery and therapy response. We aimed at developing a procedure to monitor morphological and functional parameters of the vasculature in subcutaneous xenograft models commonly applied for therapy testing by using probe-based confocal laser endomicroscopy.

Procedures

By monitoring various normal and diseased tissues, we established an experimental and analytical set-up to systematically analyze tracer extravasation from the microvasculature. Application of the approach in two xenograft models (HCT-116 and SW620) was realized consecutively throughout tumor growth.

Results

The incidence of dilated vessels increased with xenograft size in both models while macromolecule extravasation and tracer accumulation in the tumor tissue, respectively, was significantly reduced throughout growth. The development of dilated/ultradilated vessels correlated with tracer extravasation only in the HCT-116 but not the SW620 model. The underlying mechanisms are still ambiguous and discussed.

Conclusions

Our findings clearly indicate that both xenograft type and size matter for drug delivery and therapy testing.

SUBMITTER: Dietrich A 

PROVIDER: S-EPMC3826054 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature