A scientific collaboration between scientists at Georgia Tech, Emory University, the University of Massachusetts Medical School, and the University of Texas, Houston has developed a new technique to view the “leakiness” of tumors in digital mammograms. Using the technique it is possible to assess how effective a cancer medication will be once it gets to the tumor.
Georgia Tech reports:
For the study, a long-circulating nanometer-scale liposomal capsule filled with iodinated contrast agent was injected into rats with six-day-old breast cancer tumors. For the next three days, the researchers collected digital mammography images of the animals and compared the pre- and post-injection grayscale intensity values to study the dynamics of how the contrast agent accumulated in the tumor over time.
For the study, a long-circulating nanometer-scale liposomal capsule filled with iodinated contrast agent was injected into rats with six-day-old breast cancer tumors. For the next three days, the researchers collected digital mammography images of the animals and compared the pre- and post-injection grayscale intensity values to study the dynamics of how the contrast agent accumulated in the tumor over time.
“During the three-day time course, some tumors exhibited a rapid and significant increase in image brightness, meaning the contrast agent was accumulating in the tumor, whereas other tumors showed a slow and low increase,” said Bellamkonda [Ravi Bellamkonda, professor the Department of Biomedical Engineering at Georgia Tech and Emory University], who is also a Georgia Cancer Coalition Distinguished Scholar.
While the brightness of the tumors in the images changed significantly, no variations were observed in non-tumor areas or in the tumors of animals that did not receive the contrast agent. Immediately after the imaging was completed and the leakiness of each individual cancer vessel was quantified, the animals were intravenously injected with a clinically approved chemotherapy drug, liposomal doxorubicin.
Results showed that the chemotherapeutic drug slowed the progress of the tumor. The variability in uptake of the contrast agent by the tumors, as measured during the three-day imaging sessions, provided an accurate prognosis of the effect of liposomal doxorubicin on tumor growth rate.
“When we plotted the post-treatment tumor growth rate versus the intensity of leakiness, there was a significant and strong correlation,” noted Bellamkonda. “The tumors in which the nanocarrier leaked out and accumulated the most in the tumors during the initial three-day test were the ones that responded best to the treatment.”
To verify that the intensity changes in the images were caused by the nanocarrier and not endogenous changes in the tumor tissue, liposomal probes tagged with a fluorescent dye were injected into the animals. By looking at histological tumor sections, the researchers showed that the location of the increased image brightness and the fluorescent dye were the same.
“This study showed that higher uptake of the probe by the tumor related to leakier vasculature and suggested a better therapeutic outcome of liposomal doxorubicin,” said Bellamkonda. “Imaging the integrity of the tumor vasculature like this may allow cancer treatment to be more patient-specific and potentially spare patients from chemotherapy if it is not going to be effective.”
Images: Top: X-ray images showing two tumors with different levels of “leakiness”. Tumor A exhibits higher grey levels than tumor B by 40 and 70 digital units at 72 and 120 hours post-injection, respectively. Side: Fluorescent microscopy breast tumor images showing: A) Liposomes (red) in a patchy distribution in tumor periphery; B) Tumor’s highly vascularized peripheral rim (green); C) Nanocarriers (red) localized in rim.
Press release: New Technique Predicts Breast Cancer Chemotherapy Effectiveness
Abstract in Radiology…