Synthesis and Evaluation of a Targeted Nanoglobular Dual-Modal Imaging Agent for MR Imaging and Image-Guided Surgery of Prostate Cancer |
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Authors: | Mingqian Tan Zhen Ye Daniel Lindner Susann M Brady-Kalnay Zheng-Rong Lu |
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Institution: | 1. Department of Biomedical Engineering, Case Western Reserve University, Wickenden Building, Room 427, 10900 Euclid Avenue, Cleveland, Ohio, 44106-7207, USA 2. Laboratory of Biomedical Material Engineering Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, People’s Republic of China 3. Department of Translational Hematology & Oncology Research, Cleveland Clinic, Cleveland, Ohio, 44195, USA 4. Department of Molecular Biology and Microbiology School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA
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Abstract: | Purpose To synthesize and evaluate a peptide targeted nanoglobular dual modal imaging agent specific to a cancer biomarker in tumor stroma for MRI and fluorescence visualization of prostate tumor in image-guided surgery. Methods A peptide (CGLIIQKNEC, CLT1) targeted generation 2 nanoglobular (polylysine dendrimer with a silsesquioxane core) dual modal imaging agent, CLT1-G2-(Gd-DOTA-MA)-Cy5, was synthesized by stepwise conjugation of Gd-DOTA-MA, Cy5 and peptide to the dendrimer. Contrast enhanced MR imaging of the targeted dual imaging agent was evaluated on a Bruker 7T animal scanner with male athymic nude mice bearing orthotopic PC3-GFP prostate tumor. Fluorescence tumor imaging of the agent was carried out on a Maestro fluorescence imaging system. Results The targeted agent CLT1-G2-(Gd-DOTA-MA)-Cy5 produced greater contrast enhancement in the tumor tissue than the control agent KAREC-G2-(Gd-DOTA-MA)-Cy5 at a dose of 30 μmol-Gd/kg in the MR images of the tumor bearing mice. Signal-to-noise ratio (SNR) of CLT1-G2-(Gd-DOTA-MA)-Cy5 in the tumor tissue was approximately 2 fold of that of the control agent in the first 15 min post-injection. The targeted agent also resulted in bright fluorescence signals in the tumor tissue. Conclusion The CLT1 peptide targeted nanoglobular dual-imaging agent CLT1-G2-(Gd-DOTA-MA)-Cy5 has a potential for MRI and fluorescence visualization of prostate tumor. |
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