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Precision detection of liver metastasis by collagen-targeted protein MRI contrast agent. | LitMetric

AI Article Synopsis

  • The liver is a common site for metastasis in various cancers, especially uveal melanoma, which often leads to death due to late detection and limited treatment options.
  • A new contrast agent, ProCA32.collagen1, targets collagen, a key biomarker in cancer, and shows strong affinity and stability which could improve MRI imaging for early detection of liver lesions.
  • ProCA32.collagen1 has demonstrated the ability to detect very small liver micrometastases and could enhance non-invasive cancer detection and treatment planning.

Article Abstract

The Liver is the most common organ for metastasis for various cancers, including uveal melanoma, the most common primary intraocular tumor. Uveal melanoma metastasizes to the liver in ~90% of patients, and results in death in almost all cases due to late detection and lack of effective treatment. There is a pressing unmet medical need to develop MRI contrast agents and imaging methodologies with desired sensitivity and specificity to overcome the high heterogeneous background and in vivo properties as well as reduced toxicity. Herein, we report the development of a collagen targeting protein contrast agent (ProCA32.collagen1), since collagen is a diagnostic biomarker and therapeutic target for many types of primary and metastatic cancers and the tumor microenvironment. In addition to a strong affinity to collagen I, ProCA32.collagen1 possesses high relaxivities (r and r are 68.0 ± 0.25 and 100.0 ± 0.32 mM s at 1.4 T, respectively, and 42.6 ± 1.0 and 217 ± 2.4 mMs at 7.0 T per particle). ProCA32.collagen1 also has strong serum stability against degradation, resistance to transmetallation, and 10 and 10-fold higher metal selectivity for Gd over Ca and Zn, respectively, compared to clinical contrast agents. ProCA32.collagen1 does not exhibit any cell toxicity for various cell lines. Sensitive detection of liver lesions in animal models can be achieved using multiple imaging methodologies, taking advantage of the dual relaxation property of ProCA32.collagen1. ProCA32.collagen1 enables sensitive and early stage detection of hepatic micrometastasis as small as 0.144 mm and two different tumor growth patterns. Further development of ProCA32.collagen1 has the potential to greatly facilitate non-invasive, early detection and staging of primary and metastatic liver cancers, and devising effective treatments.

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Source
http://dx.doi.org/10.1016/j.biomaterials.2019.119478DOI Listing

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