Abstract
We have developed a new technique to measure in vivo tumour tissue fluid transport parameters (hydraulic conductivity and compliance) that influence the systemic and intratumoral delivery of therapeutic agents. An infusion needle approximating a point source was constructed to produce a radially symmetrical fluid source in the centre of human tumours in immunodeficient mice. At constant flow, the pressure gradient generated in the tumour by the infusion of fluid (Evans blue-albumin in saline) was measured as a function of the radial position with micropipettes connected to a servo-null system. To evaluate whether the fluid infused was reabsorbed by blood vessels, infusions were also performed after circulatory arrest. In the colon adenocarcinoma LS174T with a spherically symmetrical distribution of Evans blue-albumin, the median hydraulic conductivity in vivo and after circulatory arrest at a flow rate of 0.1 microl min(-1) was, respectively, 1.7x10(-7) and 2.3x10(-7) cm2 mmHg(-1) s. Compliance estimates were 35 microl mmHg(-1) in vivo, and 100 microl mmHg(-1) after circulatory arrest. In the sarcoma HSTS 26T, hydraulic conductivity and compliance were not calculated because of the asymmetric distribution of the fluid infused. The technique will be helpful in identifying strategies to improve the intratumoral and systemic delivery of gene targeting vectors and other therapeutic agents.
Highlights
To measure the pressure of infusion, the needle was connected to the side port of the dome of a pressure transducer (Statham 23b, Spectramed, Oxnard, CA, USA) by the PE-50 tubing, and another side port on the dome was connected by PE 50 tubing to a l-ml syringe controlled by a constant flow infusion pump (Pump 22, Harvard Apparatus, South Natick, MA, USA)
The tumours were cut to evaluate the distribution of the Evans blue-albumin complex
In other HSTS 26T tumours, the distribution of Evans blue was associated with viable tumour tissue, and it was impossible to characterize the causes of the asymmetric distribution of the Evans blue-albumin complex
Summary
The goal of the present study was, to develop a new technique to estimate K in solid tumours, in vivo, at steady state and with a good spatial resolution
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