PhD graduate student Victoria Laney analyzing the
efficacy of the targeted contrast agent for cancer imaging.
Last spring, the U.S. Food and Drug Administration approved clinical trials to test the safety of a tumor-targeting contrast agent that accurately detects aggressive prostate cancer in a magnetic resonance imaging (MRI) scan. The molecular-targeted imaging agent was invented in the lab of Zheng-Rong Lu, the M. Frank Rudy and Margaret Domiter Rudy Professor of Biomedical Engineering at Case Western Reserve University.
“Since MRI was approved for human use in the 1980s, there have been nine contrast agents approved – none of them tumor-specific,” says Lu. “We have developed the first tumor-specific contrast agent to enter clinical trials.” Clinical trials are currently underway at Ohio Clinical Trials Inc. in Columbus, Ohio, on 30 healthy males from 18 to 55 years old.
Potential for Patients
Lu began researching a system to non-invasively detect cancer nearly 20 years ago. “There is a huge clinical need for something simple and non-invasive to detect cancer at a very early stage and also to differentiate aggressive tumors from benign ones,” he says.
MRI is widely used to diagnose prostate cancer, however limitations within contrast agents added to tissues to reveal tumors can contribute to imprecise diagnosis, says Lu. Similarly, the 12-needle puncture biopsy guided by rectal ultrasound is still the most used method today to distinguish between malignant and benign tumors. “But it’s not very accurate,” says Dr. Lu. “If you don’t sample the right location, you may get wrong information.”
Approximately one in eight men will be diagnosed with prostate cancer in their lifetime, according to the American Cancer Society. However, only one in 41 will die of the disease. More than 3.1 million men are currently living with prostate cancer. These statistics highlight the importance of Lu’s work.
“Research shows that only 20% of patients diagnosed with prostate cancer will develop aggressive tumors,” he says. “Our technology has the potential to spare the other 80% from aggressive over-treatment, which could lead to serious infections and reproductive and urinary side effects.” Conversely, it could help prevent under-treatment.
The Biology Behind the Agent
The imaging agent, known as MT218, is licensed to Molecular Theranostics LLC, a Cleveland-based startup company co-founded by Lu, and its partners U.S. Motek LLC and Jiangsu Motek Pharmaceuticals Ltd. in China. The patented gadolinium-based MRI contrast agent binds to a molecular marker, called extradomain B fibronectin, which is a cancer-associated subtype of fibronectin. The gadolinium agent is a paramagnetic substance that can enhance MRI signals of aggressive tumors to improve the accuracy of cancer diagnosis.
“The technology is based on cancer biology,” says Lu. “It detects an oncoprotein that is only overexpressed in highly aggressive tumors, which is why it works so well.” Pre-clinical data is promising, says Lu, showing the agent’s efficacy and safety in animal models. “It has the potential to do what we think it can,” he adds. The goal of the ongoing clinical trials is to validate the imaging agent’s safety in humans. A phase 2 clinical trial is being pursued to test its effectiveness in detecting aggressive tumors and differentiating the types of tumors.
“We are very excited about this phase 1 clinical trial because it means our research product is now under clinical development to help people,” says Lu. “The agent was FDA-approved for prostate cancer, but its application is not limited to prostate cancer. We have shown the same technology works well for other aggressive tumors, such as breast cancer, pancreatic cancer and lung cancer.”
That’s hopeful news for the 18 million or so people worldwide who are diagnosed with cancer each year, a figure that is expected to rise to 29.5 million by 2040
PhD graduate student Victoria Laney tests the contrast agent for cancer imaging in a tumor model with a preclinical MRI scanner.
