Collaborating researchers led by a team at Hokkaido University, Japan, have developed a non-destructive cancer grade probing system (GPS) that uses a water-soluble, luminescent europium (EuIII) complex to evaluate the malignancy grade of model glioma tumor cells. The team hopes that their method could lead to development of non-invasive tests for evaluating tumor malignancy in human patients.
Headed by Yasuchika Hasegawa, PhD, and Shinya Tanaka, PhD, at Hokkaido University Institute for Chemical Reaction Design and Discovery (WPI-ICReDD), the teams’ findings were published in Scientific Reports. In their report the team concluded, “The cancer GPS, which uses a structure-changeable luminescent Eu(III) complex, provides a new analytical method for early diagnosis of human brain tumors.”
An important part of choosing the most suitable cancer therapy is understanding the malignancy of the tumor. Current methods for evaluating brain tumor malignancy are invasive and have a high risk of complications, but bioimaging technologies based on luminescent molecules are powerful approaches for locating and distinguishing tumor cells, the team noted. “Visualization of cancer cells using luminescent complexes has previously been reported, but our hypothesis was that the photophysical signals sent by such complexes in cancer cells might reflect internal information from the cancer cells,” said Hasegawa.
For their newly reported study, the investigators developed a human cancer grade probing system based on a structure-changeable Eu(III) complex, and used the technology to evaluate tumor malignancy by introducing the europium complex to model cells that mimic glioma, a common type of tumor that they say accounts for about 26.3% of brain cancers.
To develop their system the researchers first modified the europium complex so that it would be water soluble and stable among the amino acids in the DMEM (Dulbeco’s Modified Eagle Medium) cell culture medium. Upon addition to the cell culture medium, the europium complex initially forms an aggregate with itself. Interaction with model tumor cells results in the aggregates breaking into single molecules, which are then rapidly taken up by the cells. This process promotes structural changes in the europium complex, which cause changes in the lifetime of the complex’s characteristic red-light emission.
The team tested the cancer grade probing system against three different model cells that mimic different grades of malignancy. They explained, “Time-dependent emission spectra of the Eu(III) complexes in various types of tumor cells were recorded. The radiative rate constants (kr), which depend on the geometry of the Eu(III) complex, were calculated from the emission spectra.”
The results showed that during the first three hours after adding the europium complex, larger changes in the lifetime of the light emission occurred in the more malignant cells. “The tendency of the kr values to vary depended on the tumor cells at different malignancy grades,” the investigators stated. “Tumor cells with high-grade malignancy exhibited a rapid upward trend in kr values.”
The differences in emission lifetimes were attributed to differences in the tumor activity and growth processes between the three malignancy grades, which could cause different structural changes at different time scales in the europium complex. “The increasing trend of the kr values of the Eu(III) complex in tumor cells depends on the tumor malignancy grade, suggesting that different tumor activities and their growth processes may be the origin of the geometrical coordination changes of the Eu(III) complex.” The researchers anticipate that their method could be exploited to enable continuous detection of tumor activity and provide clinicians with important data to help select the most appropriate treatment. “This cancer GPS, which uses a structure-changeable luminescent Eu(III) complex, provides a new diagnostic method for determining human brain tumor.
“Brain tumors occur in 4.6 out of every 100,000 people in Japan, and the five-year survival rate is 16% for the most malignant grade 4 type of glioblastoma, which is an aggressive type of glioma brain tumor,” explained Tanaka. “The malignancy evaluation method we developed may be able to benefit these patients in the future.”