In normal subcutaneous tissue, the interstitial fluid pressure (IFP) is negative, and so, when the subcutaneous tissue of an animal is exposed, fluid does not seep out. By contrast, IFP is often increased in tumor tissue and forms a barrier against efficient drug delivery into the tumor.
Many anticancer drugs and antibodies used for treating patients with cancer are transported from the circulatory system through the interstitial space by convection (i.e. by streaming of a flowing fluid) rather than by diffusion. Increased tumor IFP causes inefficient uptake of therapeutic agents by decreasing convection. Cancer cells are therefore exposed to a lower effective concentration of therapeutic agents than normal cells, reducing treatment efficiency. Decreasing tumor IFP can thus improve drug delivery into the tumor.
AdvertisementThere are several techniques described for IFP measurements, however, all of these require experience to use ramified instrumentation and surgical procedures. Drs Ugur Ozerdem, and Alan R. Hargens, from the La Jolla Institute for Molecular Medicine, and the University of California San Diego, USA, have recently developed a simplified procedure using a transducer-tipped catheter and a precision glide needle that allows reliable measurement of IFP in tumor tissues.
This novel procedure, using a polyurethane transducer-tipped catheter (Millar), allows reliable measurement of interstitial fluid pressure (IFP) in cancer tissues. Before and after each use, the transducer is calibrated at 37°C by a water column. After calibration, the transducer is passed through the lumen of a surgical needle. The sensor is kept in the lumen of the needle during penetration into the tumor. The sensor tip is then introduced into the center core of the tumor as the needle sleeve is withdrawn from the tumor surface.
This new technique, described in Microvascular Research (available online 31 August 2005), is simple and provides IFPs equal to those provided by the well-established, wick-in-needle technique. Using this new technique, the authors compared IFP in skin melanoma grafts in NG2 knockout and wild-type mice. Knocking out NG2 proteoglycan on vasculogenic and angiogenic pericytes was found to reduce interstitial fluid pressure in melanoma. This study also demonstrates that IFP is elevated in skin melanoma.
The simplified IFP measurement procedure described in this report will allow the basic researchers and clinicians to apply IFP measurement easily and widely as a useful tool in their research.