Method of imaging lymphatic system using nanocapsule compositions

Abstract

A composition is provided accompanying nonoparticles having diameters in the range of about 100 to 800 nanometers with hollow cores and outer shells with mechanical properties such that they rupture on exposure to predetermined ultrasound energy. The composition is useful for identifying sentinel lymph nodes.

Description

[0001] This invention relates to hollow gas-filled nanoparticles in a size range optimized for uptake by the lymphatic system and to their method of use in identifying sentinel lymph nodes around tumors by means of echographic imaging techniques. BACKGROUND OF THE INVENTION [0002] Solid tumor cancers often spread through lymph channels to regional lymph nodes. Because of this tendency, elective lymph node dissection has become a recognized treatment for patients with early stage melanoma, breast, and other cancers. Many surgeons believe that elective lymph node dissection in a patient with micrometastases can prolong the patient's life and, if conducted early enough, cure the disease. Elective lymph node dissection, however, benefits only those patients with micrometastases and is unnecessary in many cases. This is a matter of concern because dissection of the entire lymphatic drainage basin is a major surgical procedure associated with a number of potential short- and long-term com...

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Problems solved by technology

Elective lymph node dissection, however, benefits only those patients with micrometastases and is unnecessary in many cases.

This is a matter of concern because dissection of the entire lymphatic drainage basin is a major surgical procedure associated with a number of potential short- and long-term complications including increased surgical trauma and scarring, risk of nerve damage, possible reduced immune system function, and lymphedema.

These technologies can only detect the presence of a sizeable, well-defined tumor mass and have not been routinely applied to the identification of the sentinel nodes.

However, application of this imaging modality for sentinel node identification has not heretofore been considered because an ultrasonic contrast agent with the necessary size spectrum and acoustic properties has yet to be described.

Larger bubbles, though more easily detected, fail to pass through the capillary network and smaller bubbles, though unrestrained by the capillary network, are detected poorly.

Microbubbles in the 1 to 10 micron size range, however, are not suitable for use in the lymphatic system.

There is as yet no consensus on the optimal radiopharmaceutical agent for sentinel node identification.

Solid and liquid particles, and particularly those less than a micron in diameter, have been shown to be poor backscatterers of ultrasound and hence have not traditionally been useful as echographic contrast agents.

Air trapping particles of a size range of less than about 900 nanometers, while potentially superior to solid or liquid nanoparticles, presents special challenges not only in their manufacture but also for optimizing a lymphatic ultrasound contrast agent due to the influence of size on its acoustic properties.

However, due to a of this rapid drop-off of signal with diameter, signal levels can quickly fall below the measurement threshold.

Thus backscatter from intact nanobubbles normally cannot be detected.

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