Neil Robertson1,2,3, Lorenzo Sempere1,2,3, Elizabeth Kenyon1,3, Christiane Mallet2,3,4, Kylie Smith3,4,5, Jeremy Hix2,3,4, Alan Halim1,3, Jinda Fan2,3,4,5, Anna Moore6,7,8. 1. Precision Health Program, Michigan State University, 766 Service Road, East Lansing, MI, 48824, USA. 2. Department of Radiology, College of Human Medicine, Michigan State University, 766 Service Road, East Lansing, MI, 48824, USA. 3. Department of Chemistry, College of Natural Sciences, Michigan State University, 578 S Shaw Lane, East Lansing, MI, 48824, USA. 4. Institute for Quantitative Health Science and Engineering, Michigan State University, 775 Woodlot Drive, East Lansing, MI, 48824, USA. 5. Department of Biomedical Engineering, College of Engineering, Michigan State University, 766 Service Road, East Lansing, MI, 48824, USA. 6. Precision Health Program, Michigan State University, 766 Service Road, East Lansing, MI, 48824, USA. moorea57@msu.edu. 7. Department of Radiology, College of Human Medicine, Michigan State University, 766 Service Road, East Lansing, MI, 48824, USA. moorea57@msu.edu. 8. Department of Chemistry, College of Natural Sciences, Michigan State University, 578 S Shaw Lane, East Lansing, MI, 48824, USA. moorea57@msu.edu.
Abstract
PURPOSE: Individual imaging modalities have certain advantages, but each suffers from drawbacks that other modalities may overcome. The goal of this study was to create a novel contrast agent suitable for various imaging modalities that after a single administration can bridge and strengthen the collaboration between the research fields as well as enrich the information obtained from any one modality. PROCEDURES: The contrast agent platform is based on dextran-coated iron oxide nanoparticles (for MRI and MPI) and synthesized using a modified co-precipitation method, followed by a series of conjugation steps with a fluorophore (for fluorescence and photoacoustic imaging), thyroxine (for CT imaging), and chelators for radioisotope labeling (for PET imaging). The fully conjugated agent was then tested in vitro in cell uptake, viability, and phantom studies and in vivo in a model of intraductal injection and in a tumor model. RESULTS: The agent was synthesized, characterized, and tested in vitro where it showed the ability to produce a signal on MRI/MPI/FL/PA/CT and PET images. Studies in cells showed the expected concentration-dependent uptake of the agent without noticeable toxicity. In vivo studies demonstrated localization of the agent to the ductal tree in mice after intraductal injection with different degrees of resolution, with CT being the best for this particular application. In a model of injected labeled tumor cells, the agent produced a signal with all modalities and showed persistence in tumor cells confirmed by histology. CONCLUSIONS: A fully functional omniparticle contrast agent was synthesized and tested in vitro and in vivo in two animal models. Results shown here point to the generation of a potent signal in all modalities tested without detrimental toxicity. Future use of this agent includes its exploration in various models of human disease including image-guided diagnostic and therapeutic applications.
PURPOSE: Individual imaging modalities have certain advantages, but each suffers from drawbacks that other modalities may overcome. The goal of this study was to create a novel contrast agent suitable for various imaging modalities that after a single administration can bridge and strengthen the collaboration between the research fields as well as enrich the information obtained from any one modality. PROCEDURES: The contrast agent platform is based on dextran-coated iron oxide nanoparticles (for MRI and MPI) and synthesized using a modified co-precipitation method, followed by a series of conjugation steps with a fluorophore (for fluorescence and photoacoustic imaging), thyroxine (for CT imaging), and chelators for radioisotope labeling (for PET imaging). The fully conjugated agent was then tested in vitro in cell uptake, viability, and phantom studies and in vivo in a model of intraductal injection and in a tumor model. RESULTS: The agent was synthesized, characterized, and tested in vitro where it showed the ability to produce a signal on MRI/MPI/FL/PA/CT and PET images. Studies in cells showed the expected concentration-dependent uptake of the agent without noticeable toxicity. In vivo studies demonstrated localization of the agent to the ductal tree in mice after intraductal injection with different degrees of resolution, with CT being the best for this particular application. In a model of injected labeled tumor cells, the agent produced a signal with all modalities and showed persistence in tumor cells confirmed by histology. CONCLUSIONS: A fully functional omniparticle contrast agent was synthesized and tested in vitro and in vivo in two animal models. Results shown here point to the generation of a potent signal in all modalities tested without detrimental toxicity. Future use of this agent includes its exploration in various models of human disease including image-guided diagnostic and therapeutic applications.
Authors: Elisabeth G E de Vries; Laura Kist de Ruijter; Marjolijn N Lub-de Hooge; Rudi A Dierckx; Sjoerd G Elias; Sjoukje F Oosting Journal: Nat Rev Clin Oncol Date: 2019-04 Impact factor: 66.675
Authors: Elaine Y Yu; Mindy Bishop; Bo Zheng; R Matthew Ferguson; Amit P Khandhar; Scott J Kemp; Kannan M Krishnan; Patrick W Goodwill; Steven M Conolly Journal: Nano Lett Date: 2017-02-21 Impact factor: 11.189
Authors: Moritz F Kircher; Adam de la Zerda; Jesse V Jokerst; Cristina L Zavaleta; Paul J Kempen; Erik Mittra; Ken Pitter; Ruimin Huang; Carl Campos; Frezghi Habte; Robert Sinclair; Cameron W Brennan; Ingo K Mellinghoff; Eric C Holland; Sanjiv S Gambhir Journal: Nat Med Date: 2012-04-15 Impact factor: 53.440