TY - JOUR
T1 - Precision detection of liver metastasis by collagen-targeted protein MRI contrast agent
AU - Salarian, Mani
AU - Yang, Hua
AU - Turaga, Ravi Chakra
AU - Tan, Shanshan
AU - Qiao, Jingjuan
AU - Xue, Shenghui
AU - Gui, Zongxiang
AU - Peng, Guangda
AU - Han, Hongwei
AU - Mittal, Pardeep
AU - Grossniklaus, Hans E.
AU - Yang, Jenny J.
N1 - Funding Information:
We thank Dr. David H. Lawson, Zhi-Ren Liu, and Alton Brad Farris for their discussion and advice. Dr. Michael Kirberger for carefully editing the manuscript. Dr. Khan Hekmatyar for his help in MRI data acquisition. This work was supported in part by a Molecular Basis of Disease fellowship (to M. Salarian) and National Institute of Health (NIH) Research Grants CA183376 and AA025863 (to J.J.Y.).
Funding Information:
We thank Dr. David H. Lawson, Zhi-Ren Liu, and Alton Brad Farris for their discussion and advice. Dr. Michael Kirberger for carefully editing the manuscript. Dr. Khan Hekmatyar for his help in MRI data acquisition. This work was supported in part by a Molecular Basis of Disease fellowship (to M. Salarian) and National Institute of Health ( NIH ) Research Grants CA183376 and AA025863 (to J.J.Y.).
Publisher Copyright:
© 2019 Elsevier Ltd
PY - 2019/12
Y1 - 2019/12
N2 - 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 (r1 and r2 are 68.0 ± 0.25 and 100.0 ± 0.32 mM−1 s−1 at 1.4 T, respectively, and 42.6 ± 1.0 and 217 ± 2.4 mM−1s−1 at 7.0 T per particle). ProCA32.collagen1 also has strong serum stability against degradation, resistance to transmetallation, and 102 and 1013-fold higher metal selectivity for Gd3+ over Ca2+ and Zn2+, 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 mm2 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.
AB - 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 (r1 and r2 are 68.0 ± 0.25 and 100.0 ± 0.32 mM−1 s−1 at 1.4 T, respectively, and 42.6 ± 1.0 and 217 ± 2.4 mM−1s−1 at 7.0 T per particle). ProCA32.collagen1 also has strong serum stability against degradation, resistance to transmetallation, and 102 and 1013-fold higher metal selectivity for Gd3+ over Ca2+ and Zn2+, 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 mm2 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.
KW - Collagen I
KW - Liver metastasis
KW - Magnetic resonance imaging
KW - Protein contrast agent
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U2 - 10.1016/j.biomaterials.2019.119478
DO - 10.1016/j.biomaterials.2019.119478
M3 - Article
C2 - 31542517
AN - SCOPUS:85072298461
SN - 0142-9612
VL - 224
JO - Biomaterials
JF - Biomaterials
M1 - 119478
ER -