Article
Bi-Directional capillary permeability, regional blood volume and size of the extracellular space in brain metastases – Implications for treatment
Bi-direktionale kapilläre Permeabilität, regionales Blutvolumen und Größe des Extrazellulärraumes in Hirnmetastasen - Implikationen für die Therapie
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Authors
Published: | April 23, 2004 |
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Outline
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Objective
Cerebral metastases pose a therapeutic challenge as their vascular physiology limits the efficacy of chemotherapy and immunotherapy. We have therefore performed a quantitative study into the physiology of metastatic vasculature.
Methods
Seven patients underwent measurement of the blood-brain transfer rate (K1) the brain-blood transfer rate (K2), the plasma vascular space and the extracellular space using dynamic spiral-CT. From these measurements parameter maps with a spatial resolution of .8 x .8 x 400ml were derived and histogram analysis was performed as to the distribution of physiological variables within the tumour and surrounding brain.
Results
Mean value for the blood-brain transport were 13.98 ± 7.16 μl/gm/min with a variation from 3.1 ± 9.4 to 25.5 ± 17.9. Vascular space showed a mean of .038 ± .024 μl/gm with a variation of .015 ± .025 to .075 ± .008 ml/gm. Also the efflux constant (K2) varied considerably with a median of 59 ± 45.6 min. The extracellular space was extremely variable ranging from .13 to .7 ml/gm with a mean of .38 ± .012. There was no correlation between vascularisation and individual tumour permeability (logistic regression p>.05). Metastases were significantly less permeable than primary CNS lymphomas (p<.01).
Conclusions
Our study shows that cerebral metastases are a heterogeneous physiological entity with severely limited permeability for water-soluble drugs making them rather distinct from other extra cerebral tumours like CNS lymphomas. Also the extracellular space in these tumours is quite enlarged resulting in a ‘sink effect’ for any drug penetrating into the extracellular space of the tumour.