Researchers have developed a way to measure the leakiness of blood vessels—a predictor of chemotherapy's efficacy—using a digital mammography unit, according to a study published in the February issue of Radiology.
The purpose of the study was to prospectively predict the effectiveness of a clinically used nanochemotherapeutic agent by detecting and measuring the intratumoral uptake of an x-ray contrast agent nanoprobe in rats with six-day-old breast cancer tumors by using digital mammography.
The digital mammography-based quantification of "leakiness" is closely correlated to the ability of a chemotherapy agent to enter the tumor, allowing the researchers to predict the agent's therapeutic efficacy, they wrote.
"We developed a quantitative way to measure the leakiness of the blood vessels, which is directly linked to the amount of drug that gets to the cancer and in turn determines effectiveness," said Ravi Bellamkonda, a professor in department of biomedical engineering at Georgia Tech and Emory University in Atlanta. "By simply measuring how much contrast agent reaches the tumor, we can predict how much of a clinically approved chemotherapeutic will reach the tumor, allowing physicians to personalize the dose and predict effectiveness."
During the three-day time course, the researchers noted that 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.
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, according to the authors. 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.
"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," Bellamkonda wrote. He and colleagues plan to investigate whether the liposomal probes can be used for this purpose in the future, and whether the leakiness of tumor vasculature represents a parameter that is useful for clinical diagnosis or tumor characterization.