Protein MRI contrast agent with unprecedented metal selectivity and sensitivity for liver cancer imaging.


Author: Xue S1, Yang H2, Qiao J3, Pu F3, Jiang J4, Hubbard K4, Hekmatyar K5, Langley J6, Salarian M4, Long RC7, Bryant RG8, Hu XP6, Grossniklaus HE2, Liu ZR9, Yang JJ10.

Affiliation: 1Departments of Biology and Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303; 2Departments of Ophthalmology and. 3Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303; Inlighta Biosciences LLC, Marietta, GA 30068; 4Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303; 5Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602; 6Coulter Department of Biomedical Engineering, Georgia Tech and Emory University, Atlanta, GA 30322; and. 7Radiology, Emory University, Atlanta, GA 30322; 8Department of Chemistry, University of Virginia, Charlottesville, VA 22904. 9Departments of Biology and. 10Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303; jenny@gsu.edu.
Conference/Journal: Proc Natl Acad Sci U S A.
Date published: 2015 May 25
Other:
 Volume ID: 112   ,  Issue ID: 21   ,  Pages: 6607-12   ,  Special Notes: doi: 10.1073/pnas.1423021112   ,  Word Count: 281  
    

With available MRI techniques, primary and metastatic liver cancers that are associated with high mortality rates and poor treatment responses are only diagnosed at late stages, due to the lack of highly sensitive contrast agents without Gd(3+) toxicity. We have developed a protein contrast agent (ProCA32) that exhibits high stability for Gd(3+) and a 10(11)-fold greater selectivity for Gd(3+) over Zn(2+) compared with existing contrast agents. ProCA32, modified from parvalbumin, possesses high relaxivities (r1/r2: 66.8 mmol(-1)⋅s(-1)/89.2 mmol(-1)⋅s(-1) per particle). Using T1- and T2-weighted, as well as T2/T1 ratio imaging, we have achieved, for the first time (to our knowledge), robust MRI detection of early liver metastases as small as ∼0.24 mm in diameter, much smaller than the current detection limit of 10-20 mm. Furthermore, ProCA32 exhibits appropriate in vivo preference for liver sinusoidal spaces and pharmacokinetics for high-quality imaging. ProCA32 will be invaluable for noninvasive early detection of primary and metastatic liver cancers as well as for monitoring treatment and guiding therapeutic interventions, including drug delivery.

KEYWORDS:

MRI; T2/T1 ratio imaging; contrast agents; metastasis; uveal melanoma

PMID: 25971726



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New MRI Approach Detects Early Liver Tumors in Mouse Model of Human Disease

Scientists at Georgia State University (GSU) with funding from the National Institute of Biomedical Imaging and Bioengineering (NIBIB) have designed an imaging technique to detect early-stage liver tumors, and have proven it successful in mice. Their study in an animal model is an essential step toward creating tools to improve liver tumor detection in human patients—whether primary liver cancer or metastatic tumors that arise in liver but have spread from other tissue.