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

Salarian, Mani; Yang, Hua; Turaga, Ravi Chakra; Tan, Shanshan; Qiao, Jingjuan; Xue, Shenghui; Gui, Zongxiang; Peng, Guangda; Han, Hongwei; Mittal, Pardeep; Grossniklaus, Hans E.; Yang, Jenny J.

doi:10.1016/j.biomaterials.2019.119478

Cited by 21 publications

(27 citation statements)

References 43 publications

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“…More specifically, the upregulation of collagen as the most abundant ECM component appears to play a prominent role in the tumor activating orchestra. For primary [ 7 , 8 ] and secondary [ 1 , 9 , 10 ] liver cancers, it has been shown that collagen upregulation seems to play a substantial role in angiogenesis, tumor cell infiltration and thus sensitivity to anticancer agents.…”

Section: Introductionmentioning

confidence: 99%

Native T1 Mapping Magnetic Resonance Imaging as a Quantitative Biomarker for Characterization of the Extracellular Matrix in a Rabbit Hepatic Cancer Model

et al. 2020

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To characterize the tumor extracellular matrix (ECM) using native T1 mapping magnetic resonance imaging (MRI) in an experimental hepatic cancer model, a total of 27 female New Zealand white rabbits with hepatic VX2 tumors were examined by MRI at different time points following tumor implantation (day 14, 21, 28). A steady-state precession readout single-shot MOLLI sequence was acquired in a 3 T MRI scanner in prone position using a head-neck coil. The tumors were segmented into a central, marginal, and peritumoral region in anatomical images and color-coded T1 maps. In histopathological sections, stained with H&E and Picrosirius red, the regions corresponded to central tumor necrosis and accumulation of viable cells with fibrosis in the tumor periphery. Another region of interest (ROI) was placed in healthy liver tissue. T1 times were correlated with quantitative data of collagen area staining. A two-way repeated-measures ANOVA was used to compare cohorts and tumor regions. Hepatic tumors were successfully induced in all rabbits. T1 mapping demonstrated significant differences between the different tumor regions (F(1.43,34.26) = 106.93, p < 0.001) without interaction effects between time points and regions (F(2.86,34.26) = 0.74, p = 0.53). In vivo T1 times significantly correlated with ex vivo collagen stains (area %), (center: r = 0.78, p < 0.001; margin: r = 0.84, p < 0.001; peritumoral: r = 0.73, p < 0.001). Post hoc tests using Sidak’s correction revealed significant differences in T1 times between all three regions (p < 0.001). Native T1 mapping is feasible and allows the differentiation of tumor regions based on ECM composition in a longitudinal tumor study in an experimental small animal model, making it a potential quantitative biomarker of ECM remodeling and a promising technique for future treatment studies.

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Section: Introductionmentioning

confidence: 99%

Native T1 Mapping Magnetic Resonance Imaging as a Quantitative Biomarker for Characterization of the Extracellular Matrix in a Rabbit Hepatic Cancer Model

et al. 2020

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“…This approach enables us to add molecular specificity, without sacrificing metal binding and relaxivity properties (Pu et al, ; Qiao et al, ; Wei et al, ). In addition, we have developed a collagen targeted protein contrast agent, ProCA32.collagen1 (Salarian, Turaga, et al, ; Salarian, Yang, et al, ) by engineering a collagen type I targeting moiety to the C‐terminal of protein contrast agent, ProCA32 (with two Gd 3+ binding sites). In the modeled structure, lysine residues are positioned as anchor points for PEG modification.…”

Section: Design Of Targeted Contrast Agents Using Proteinsmentioning

confidence: 99%

“…In the modeled structure, lysine residues are positioned as anchor points for PEG modification. A flexible hinge was used to maximize targeting capacity and relaxivity, while maintaining metal binding capability (Salarian, Turaga, et al, ; Salarian, Yang, et al, ). PEGylation was used to improve relaxivities by tuning correlation time.…”

Section: Design Of Targeted Contrast Agents Using Proteinsmentioning

confidence: 99%

“…ProCA32.collagen1 was developed by covalently linking a collagen type I targeting peptide moiety consisting of natural amino acids to the C‐terminal of protein contrast agent ProCA32 (with two Gd 3+ binding sites). PEGylation of the contrast agent was performed to improve protein solubility, blood retention time, and reduce immunogenicity (Salarian, Turaga, et al, ; Salarian, Yang, et al, )…”

Section: Design Of Targeted Contrast Agents Using Proteinsmentioning

confidence: 99%

“…It is worth mentioning that the majority of small Gd 3+ ‐binding chelators have weak metal selectivity for Gd 3+ over physiological metal ions such as Ca 2+ , Zn 2+ , and Mg 2+ . Our developed protein‐based MRI contrast agents, with higher metal selectivity, exhibit strong advantages over these small chelators (Pu et al, ; Pu, Salarian, et al, ; Salarian, Turaga, et al, ; Salarian, Yang, et al, ; Xue et al, ). Moreover, it is essential to ensure that metal binding affinity and relaxivity of targeted contrast agents are not reduced upon addition of a targeting moiety.…”

Section: Barriers In Clinical Translation Of Mri Contrast Agentsmentioning

confidence: 99%

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Molecular imaging of extracellular matrix proteins with targeted probes using magnetic resonance imaging

Salarian

Ibhagui

Yang

2020

WIREs Nanomed Nanobiotechnol

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The extracellular matrix (ECM) consists of proteins and carbohydrates that supports different biological structures and processes such as tissue development, elasticity, and preservation of organ structure. Diseases involving inflammation, fibrosis, tumor invasion, and injury are all attributed to the transition of the ECM from homeostasis to remodeling, which can significantly change the biochemical and biomechanical features of ECM components. While contrast agents have played an indispensable role in facilitating clinical diagnosis of diseases using magnetic resonance imaging (MRI), there is a strong need to develop novel biomarker‐targeted imaging probes for in vivo visualization of biological processes and pathological alterations at a cellular and molecular level, for both early diagnosis and monitoring drug treatment. Herein, we will first review the pathological accumulation and characterization of ECM proteins recognized as important molecular features of diseases. Developments in MRI probes targeting ECM proteins such as collagen, fibronectin, and elastin via conjugation of existing contrast agents to targeting moieties and their applications to various diseases, are also reviewed. We have also reviewed our progress in the development of collagen‐targeted protein MRI contrast agent with significant improvement in relaxivity and metal binding specificity, and their applications in early detection of fibrosis and metastatic cancer. This article is categorized under: Diagnostic Tools > in vivo Nanodiagnostics and Imaging Biology‐Inspired Nanomaterials > Peptide‐Based Structures Biology‐Inspired Nanomaterials > Protein and Virus‐Based Structures

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Recent Trends in Diagnostic Biomarkers of Tumor Microenvironment

et al. 2022

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

Cited by 21 publications

References 43 publications

Native T1 Mapping Magnetic Resonance Imaging as a Quantitative Biomarker for Characterization of the Extracellular Matrix in a Rabbit Hepatic Cancer Model

Native T1 Mapping Magnetic Resonance Imaging as a Quantitative Biomarker for Characterization of the Extracellular Matrix in a Rabbit Hepatic Cancer Model

Molecular imaging of extracellular matrix proteins with targeted probes using magnetic resonance imaging

Recent Trends in Diagnostic Biomarkers of Tumor Microenvironment

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