The major barriers limiting the application of MRI to detect small liver lesions and metastasis at the early stage and patient selection for targeted therapy based on molecular imaging of disease biomarkers, are due to the lack of desired MRI contrast agents capable of enhancing the contrast between normal liver tissues and tumors with high relaxivity, tumor targeting, high intra-tumoral distribution and no toxicity. The low sensitivty related to low relaxivity of the current clinically approved contrast agents has posted additional limitations to the further application of MRI to monitor the effect of metastasis treatment, including image-guided laser ablation. To address the critical need, We (Dr. Jenny J. Yang's team in Atlanta) have developed a novel class of protein-based MRI contrast agents which exhibit significant improvement of both r1 and r2 relaxivities compared to the clinical MRI contrast agents, an improvement in in vivo dose efficiency in mouse models, is capable of in vivo imaging with T2/T1 ratiometric changes, and low toxicity and immunogenicity. The goal of STTR Phase I research is to obtain proof-of- principle evidence to achieve early detection of liver tumor and metastasis of uveal melanoma with significantly improved sensitivity and selectivity by optimizing and characterizing our designed protein-based contrast agents (ProCAs) with liver preference and tumor specificity.
Aim 1 is to develop liver-specific tumor imaging contrast agents with desired stability and sensitivity using a transplanted mouse model.
Aim 2 is to develop liver tumor-specific molecular imaging contrast agent with high accuracy using transplanted and orthotropic melanoma metastasis models. Comparisons with clinically approved MRI contrast agent Eovist/Primost and detailed histology analysis will be performed. In Phase II studies, we will investigate safety, immunogenicity, and their effectiveness in monitoring responses to targeted therapies and application to image-guided surgery. These proposed studies will provide necessary results for transition to clinical application for liver metastasis.
The goal of STTR Phase I research is to obtain proof-of-principle evidence to achieve early detection of liver tumor and metastasis of uveal melanoma with significantly improved sensitivity and selectivity by optimizing and characterizing our designed protein-based contrast agents (ProCAs) with liver preference and tumor specificity. Our proposed studies to improve the liver tumor imaging with unprecedented relaxivity, targeting capability and good liver and tumor tissue distribution of the designed contrast agents will fill i a major market need in clinical applications facilitating development of novel targeted therapies with improved accuracy and reduced detection errors.
|Xue, Shenghui; Yang, Hua; Qiao, Jingjuan et al. (2015) Protein MRI contrast agent with unprecedented metal selectivity and sensitivity for liver cancer imaging. Proc Natl Acad Sci U S A 112:6607-12|