INTRATUMORAL INFUSION OF FLUID - ESTIMATION OF HYDRAULIC CONDUCTIVITYAND IMPLICATIONS FOR THE DELIVERY OF THERAPEUTIC AGENTS

We have developed a new technique to measure in vivo tumour tissue flu id transport parameters (hydraulic conductivity and compliance) that i nfluence the systemic and intratumoral delivery of therapeutic agents. An infusion needle approximating a point source was constructed to pr oduce a radially symmetrical fluid source in the centre of human tumou rs in immunodeficient mice. At constant flow, the pressure gradient ge nerated in the tumour by the infusion of fluid (Evans blue-albumin in saline) was measured asa function of the radial position with micropip ettes 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 s pherically symmetrical distribution of Evans blue-albumin, the median hydraulic conductivity in vivo and after circulatory arrest at a flow rate of 0.1 mu l min(-1) was, respectively, 1.7x10(-7) and 2.3x10(-7) cm(2) mmHg(-1) s. Compliance estimates were 35 mu l mmHg(-1) in vivo, and 100 mu l mmHg(-1) after circulatory arrest. In the sarcoma HSTS 26 T, hydraulic conductivity and compliance were not calculated because o f 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 agen ts.