A new imaging agent appears capable of
distinguishing aggressive from benign prostate cancer, potentially helping doctors select with better precision those patients in need of more extensive treatment, a pre-clinical study finds.
So far only tested in mice, the imaging agent makes use of a newly identified protein only present in aggressive prostate cancer forms. A more precise way of diagnosing
this type of prostate cancer would both allow early treatment of those in need, and spare patients with slow-growing tumors unnecessary side effects.
In addition, the imaging method could be used to monitor patients with slow-growing tumors for changes, detecting if a
tumor turns aggressive.
The study, “Targeted Contrast Agent Specific to an Oncoprotein in Tumor Microenvironment with the Potential for Detection and Risk Stratification of Prostate Cancer with MRI,” was published in the journal Bioconjugate Chemistry.
Earlier studies have linked the protein, named EDB-FN (extradomain B fibronectin), to metastases and treatment-resistance in other cancers. This led researchers at Case Western Reserve University and the Cleveland Clinic to explore the protein in prostate cancer. They noted it was a driver of aggressive prostate cancer growth.
To evaluate this finding, they developed a compound that bound specifically to EDB-FN. They then linked it to a contrast enhancement agent used in magnetic resonance imaging (MRI), so an MRI scan of the prostate would light up only aggressive tumors.
Testing the method in mice injected with human prostate cancer cells, the team
verified that the compound, which they called ZD2-Gd, only bound to aggressive cancer cells. In mice with slow-growing cancers, the tumor did not show up on MRI images.
“The key is to differentiate clinically significant, high-risk tumors that need treatments from those low-risk tumors that do not require treatment, which will spare many patients from unnecessary, expensive and invasive procedures,” Guoying Lu, PhD, director of the program in magnetic resonance imaging at the National Institute of Biomedical Imaging and Bioengineering, which funded the study, said in a press release.
Prostate cancer strikes one in seven men, but only about 20% of those with prostate cancer have a life-threatening tumor needing aggressive treatment. The other 80% have slow-growing tumors that require little to no treatment.
The team also performed experiments to see if the ZD2-Gd compound was effectively cleared from mice after use. Gd is short for gadolinium — a contrast agent that is routinely used in healthcare. But recent research has indicated that gadolinium may remain in the body, particularly in patients undergoing repeated MRI scans.
The team compared the time it took for the ZD2-Gd contrast agent to be cleared out of the body following injection compared to gadolinium as a sole contrast agent. They noted no difference.
Analyses of mice tissue one week after injection also showed that there was no ZD2-Gd remaining, meaning
healthy tissue would not continue to be affected by its use.
“Not only does ZD2-Gd bind specifically to the high-grade prostate cancer cells, but it binds so well that it can detect even early stage tumors of small numbers of these cells. This means we can potentially use MRI to non-invasively find those individuals with the high-grade tumors and find them early when treatment has a much higher chance of being effective,” said Zheng-Rong Lu, PhD, senior author of the study and a professor of biomedical engineering at Case Western.