Margaret A Wheatley
Drexel University, USA
Title: Molecular oxygen delivery to hypoxic tumors by ultrasound triggering
Biography
Biography: Margaret A Wheatley
Abstract
Hypoxia in tumors inhibits sensitivity to radiation therapy. We studied the delivery of oxygen to tumors using an ultrasound-sensitive microbubble platform developed at Drexel consisting of a mixed surfactant shell surrounding either oxygen (SE61O2) or nitrogen (SE61N2). Oxygen release kinetics was measured using an Oxy Lite 2000 bare fiber pO2 probe. In vitro ultrasound used a Sonix RP scanner with a PA4-2 probe in power Doppler mode. Samples in 100 ml degassed saline were triggered over 20 minutes (readings obtained every 30s). In vivo proof of concept (two mice with MDA-MB-231 breast tumor xenografts) introduced the probe into the tumor via 21G catheter. Flash-replenishment imaging at the fiber tip was performed using a Vevo 2100 scanner in nonlinear imaging mode at 18 MHz during IV injection of 0.05 ml of agent. Partial oxygen pressures were recorded every 5s until returned to baseline. Release profiles were compared to untriggered SE61O2, and triggered SE61N2. Two ml of SE61O2 triggered with ultrasound elevated oxygen partial pressures of 100 ml of degassed saline 13.8 mmHg more than untriggered bubbles and 20.6 mmHg more than triggered nitrogen-filled bubbles. In vivo controls produced no discernible increase in oxygen partial pressure except for a brief (25s) 5.6 mmHg increases in one animal. Ultrasound triggered SE61O2 resulted in a 30.4 mmHg increase in one tumor, with elevated tumor oxygen levels lasting over 4 minutes, and an increase of 27.4 mmHg, with elevated tumor oxygen levels lasting 1.7 minutes in the second. We conclude that in vivo elevation of tumor oxygenation levels using SE61O2 appears feasible but highly tumor dependent.