Tiny gas microbubbles may enhance the delivery and absorption of cancer drugs in patients with advanced pancreatic cancer, according to a pilot study described today at the International Contrast Ultrasound Society (ICUS) annual conference.
“These preliminary findings are extremely exciting because this study appears to represent the first time ultrasound microbubbles have been used in patients for drug delivery”
"Our early findings suggest that commercially-available ultrasound microbubbles, combined with a standard chemotherapy drug, may prolong survival in pancreatic cancer patients," according to Dr. Odd Helge Gilja, Head of National Centre of Ultrasound in Gastroenterology at Haukeland University Hospital, Chair of Research at Dept. Of Clinical Medicine at University of Bergen, Norway, and President-Elect of the European Federation of Ultrasound in Medicine and Biology.
The pilot study included 10 patients with inoperable tumors, and preliminary results showed that tumor size was reduced or growth was slowed in the patients, according to Dr. Gilja. Additional studies are planned to confirm and potentially extend the results, he said.
"These preliminary findings are extremely exciting because this study appears to represent the first time ultrasound microbubbles have been used in patients for drug delivery," according to Dr. Steven Feinstein, Co-President of ICUS and a professor of medicine at Rush University, Chicago. "If further studies confirm the Bergen findings, ultrasound microbubbles could prove to be an innovative platform option for delivery of drugs and genes to treat other cancers and a wide variety of medical abnormalities throughout the body," he said.
The microbubbles were initially developed as diagnostic ultrasound contrast agents, according to Dr. Feinstein.
"Whenever an ultrasound image is too grainy or too fuzzy to be interpretable, a microbubble ultrasound contrast agent may be used to sharpen the image, improve the reliability of the scan and reduce the need for unnecessary downstream testing," he said.
Ultrasound contrast agents consist of liquid suspensions of tiny gas-filled microbubbles that are injected into the patient's arm vein during an ultrasound scan, according to Dr. Stephanie Wilson, Co-President of ICUS and a radiologist from the University of Calgary. A few drops of the microbubbles efficiently reflect ultrasound signals as they flow through the microcirculation and are expelled from the body within minutes, she said.
"Ultrasound contrast agents are safe, convenient, completely radiation-free, and routinely used by physicians throughout the world to obtain a reliable ultrasound diagnosis," according to Dr. Wilson.
The Norwegian study appears to extend the use of ultrasound microbubbles from diagnostic imaging to therapeutic drug delivery.
Dr. Gilja reported that all 10 patients who participated in the pilot Phase I study received an infusion of a standard chemotherapy drug, gemcitabine, followed by an infusion of Sonovue (Bracco), a microbubble contrast agent available for diagnostic imaging in Europe. A customized commercial ultrasound scanner was then used to confirm the presence of Sonovue in the vicinity of the tumor and to induce "sonoporation," a transient opening and resealing of cell membranes to allow for enhanced delivery and absorption of the cancer drug. Tumor sizes were confirmed by CT imaging, according to Dr. Gilja.
Two ultrasound contrast agents, Definity (Lantheus Medical Imaging) and Optison (GE Healthcare), are available in the United States but are approved by the Food and Drug Administration for cardiac imaging only. Ultrasound contrast agents, including Sonovue, are approved by regulatory agencies in Europe, Asia and elsewhere for a broader range of diagnostic uses, including imaging of tumors and organ systems throughout the body. Additional diagnostic uses are being reviewed by regulatory agencies but therapeutic applications of ultrasound contrast agents have not yet been submitted for review.