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Novel protein class aids in detection of early-stage liver cancer

Researchers have, for the first time ever, developed a protein that enables noninvasive detection of early-stage liver metastases — as small as approximately 0.24 in diameter — in patients at high-risk for primary and metastatic liver cancers, according to study findings.

Jenny Yang, PhD, associate director of the Center for Diagnostics and Therapeutics at Georgia State University, and colleagues sought to test new ways to earlier diagnose and effectively treat small tumors in high-risk primary and metastatic liver cancers. They aimed to develop MRI agents with improvements in sensitivity, metal stability and pharmacokinetics for the earlier detection of small tumors.

Jenny Yang

“Liver cancers associated with high mortality rates and poor treatment responses are often diagnosed in the late stages because there is not a reliable way to detect primary liver cancer and metastasis at a size smaller than one centimeter,” Yang said in a press release.

The MRI contrast agent, ProCA32, was used in a mouse model to test the ability to increase relaxivity, but without altering the stability and selectivity of metal binding or altering properties of pharmacokinetics.    

Yang and colleagues proved that “by protein design and modification [with] unprecedented metal selectivity and improved blood, liver and kidney pharmacokinetics,” the ProCA32 MRI contrast agent detected hepatic metastases of early-stage uveal melanoma. 

ProCA32 exhibited high stability for Gd³⁺ and a 10¹¹-fold greater selectivity for Gd³⁺ over Zn²⁺ compared with existing contrast agents, according to the research. ProCA32 possessed high relaxivities when it was modified from parvalbumin.

“Our new agents can obtain both positive and negative contrast images within one application, providing double the accuracy and confidence of locating cancerous tumors,” Yang said. “These agents are also expected to be much safer with reduced metal toxicity.”

The new agents could also assist in the imaging of multiple organs, including kidney and blood vessels, as well as liver and tumors, according to the release.

“ProCA32 may have far-reaching implications in the diagnosis of other malignancies, which in turn would facilitate development of targeted treatment along with effective monitoring of reduction of tumor burden,” Yang said. “Our agent and methodology can also be applied to study the brain and monitor treatment outcomes in a number of disorders, including stroke and recovery after stroke, Alzheimer's disease, brain tumors and gliomas.”

Disclosure: The researchers report no relevant financial disclosures.