Assessing Drug Delivery and Resistance to Therapy of Tumor by MRI (Yeda)
A non invasive method for determining the interstitial fluid pressure (IFP) in tumors.
The majority of cancer diseases are managed with a variety of systemic therapeutic agents. These agents are usually administered through the blood circulation, enter the tumor vasculature, extravasate out into the tissue across the microvascular wall and move through the interstitial compartment into the cells overcoming the cells membrane barrier. However, these therapeutic agents may not reach the target cells because of high pressure gradients that do not allow entrance of the drug to the tumor. This inhibition of delivery of drugs is a form of a physical drug resistance and can drastically impair treatment of tumors.
This invention present an MRI imaging method for non-invasively monitoring an actual system pressure, assessing drug delivery and resistance to therapy of a tumor or organ, control pressure in a tumor or organ and mapping delivery capacity by imaging actual interstitial fluid pressure and concentration or distribution of a tracer.In order to map interstitial fluid pressure and barriers to drug delivery, a contrast agent is administered by a slow infusion into the blood circulation of a mammal while monitoring by MRI the concomitant changes in signal enhancement. When the concentration of the contrast agent in the blood circulation reaches a steady state, the monitoring by MRI produces output images indicative of changes in contrast agent concentration in the system that are processed according to a novel algorithm to obtain data regarding transfer constants and values of pressure gradients, and to obtain data regarding the differences in space between the distribution of the tracer due to the presence of pressure gradients. Essentially, the interstitial fluid pressure (IFP) can be determined and monitored in an ongoing basis, so that the effective transcapillary transfer through the interstitium from adjacent regions is known, while giving an indication of delivery of or resistance to delivery of a drug to a tumor or organ.
An imaging method that can measure pressure not just in a limited loci of a tumor.
A non-invasive method which does not damage the investigated tissue and which does not elevating the interstitial fluid pressure of the investigated tissue.
Can be used for internal organs and tumors.
Monitor temporal changes in interstitial fluid pressure.
Assessing a tumor's susceptibility and resistance to drugs.
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