A team of scientists from Georgia State University (GSU), funded by National Institute of Biomedical Imaging and Bioengineering (NIBIB) have presented a new way of MRI scan that can detect early stage hepatic tumors. The method was already proven to be effective in studies on mice. Recreation a disease in an animal model is one of important steps for later implementation of the method in human medicine practice. The goal of the method is to detect small scale primary or secondary (metastatic) liver tumors.

When the cancer is detected at an early stage, the odds of successful treatment and actually surviving it are much higher. This is very important, as liver cancer is usually detected at a pretty advanced stage, and is accounted for almost 25,000 fatal outcomes throughout US every year.

The article, published on May 11, 2015 in Proceedings of the National Academy of Sciences, the senior author Jenny Yang, prof. of biochemistry and biophysics at GSU (also an associate director of GSU’s Center for Diagnostics and Therapeutics) and his team introduced their enhancement for the MRI, a specific protein­based contrast material. 

The MRI creates high­resolution images of tissue using a magnetic field and radio ways. To carefully study the liver, a contrast medium is administered into the patient’s system. This allows a more detailed look onto the organ’s structure. However, the existing contrast solutions are not sensitive enough to highlight the small tumors and are quickly flushed out of the organ’s bloodstream. This is extremely important, because the smaller the tumor is, the better are the odds of successful treatment and recovery.

Prof. Yang says that MRI is an effective and safe method, based on non­ionizing radiation. It allows to examine small details of the soft tissues in high resolution. Thus, enhancing the MRI contrast allows the custom imaging for diagnostics, treatment and image­guided procedures. 

Dr. Yang’s team has synthesized the entire new class of protein­based contrast agents. One of them, ProCA32 has already been tested in mice and enabled much earlier detection of hepatic cancer. The new contrast is capable of highlighting a tumor .24 mm in diameter, which is close a grain of sand. The current limit for tumor detection was about one centimeter. Dr. Yang believes that this method will be an unprecedented breakthrough in liver cancer detection.

The researchers modified the ProCA32 chemistry for detectable metals to hook up with Ca molecules on specific proteins, exclusive to cancer cells. During the trial, the team used the contrast to take liver images in mice with melanoma.

Further enhancements allow to keep ProCA32 in the patient’s system for a longer period of time, which dramatically increases the window for tumor detection. The contrast also has lower effective dose in comparison to known solutions, which results in lower possibility toxic effect induction. Both positive and negative images can be obtained using this contrast, so the accuracy of the imaging is significantly increased.

Richard Conroy, Ph.D., director at NIBIB’s Division of Applied Science and Technology, says that the authors found a very sensitive and specific way of in vivo liver diagnostics and distinguished a specific molecular signature indicative for a liver tumor in an early stage. He pointed, that specificity and sensitivity are the key for an early stage diagnostics.

Dr. Yang and her team hope, that this new solution will help the specialists to diagnose various liver diseases, such as cancer, cirrhosis and fibrosis and also provide guidance during their treatment. The team is now cooperating with radiologists to make these solutions available for use in patients, who need it, and are hopeful that their product can meet the standards of the US Food and Drug Administration.

The study is supported in part by NIBIB grant EB007268, and NIH grants GM62999, CA118113, CA176001, and S10RR023706. Xue S, Yang H, Qiao J, Pu F, Jiang J, Hubbard K, Hekmatyar K, Langley J, Salarian M, Long RC, Bryant RG, Hu XP, Grossniklaus HE, Liu ZR, Yang JJ. Proc Natl Acad Sci U S A. 2015 May 26;112(21):6607­12.