Researchers have developed an ultrasound technique to image pancreatic tumors in mice, described in the October issue of Gastroenterology. This approach might useful in early detection of pancreatic ductal adenocarcinoma (PDAC).
PDAC is the fourth leading cause of cancer death in the United States. It is usually diagnosed at an advanced stage, so patients have a median survival of less than 1 year. Techniques for earlier detection of PDAC are therefore urgently needed.
Imaging agents that bind neovascular proteins in even small tumors can be detected by ultrasound. Kira Foygel et al. found that levels of thymocyte differentiation antigen (Thy1) were significantly higher in the newly formed blood vessels of PDACs than in tissues from patients with chronic pancreatitis. They investigated wehther Thy1 might be used to identify tumors.
The authors attached anti-human or anti-mouse Thy1 antibodies, or isotype-matched control antibodies (as a control), to the surface of perfluorocarbon-containing, lipid-shelled microbubbles.
Microbubbles are gas-filled contrast agents, several microns in size, that can be modified to bind specific targets. After intravenous injection, the microbubbles accumulate at tissues containing the target,where they produce an ultrasound imaging signal.
In transgenic mice that develop pancreatic cancer, the Thy1-targeted microbubbles produced a much stronger ultrasound signal at tumors (as small as 2 mm) than control microbubbles. Also, the imaging signal was significantly higher in pancreatic tumors than in pancreatic tissues of healthy mice or of mice with chronic pancreatitis (see left side of figure), or in the vasculature of any other organs.
The control microbubbles did not produce a significant signal at pancreatic tumors or any other tissues tested (right side of figure).
Ultrasound is one of the most promising imaging tools for detecting early-stage cancer, because it is noninvasive and inexpensive (compared with other imaging modalities), does not use ionizing irradiation, and has a high spatial and temporal resolution.
But what is Thy1, and why is it such a good PDAC marker? Thy1 is a cell-surface glycoprotein on the surface of newly formed blood vessels, colon tumors, glioblastomas, hepatocellular carcinomas, and ovarian cancer tissues. Foygel et al. detected Thy1 on the neovasculature of 81% of human PDACs, but very low levels in normal pancreatic tissue or chronic pancreatitis tissues from humans and mice.
The authors state that because ultrasound is safe, inexpensive, and widely available, it might eventually be to screen patients for early-stage PDACs.