Molecular imaging to quantify tumor receptor activity has incredible potential for imaging extracellular protein signaling, yet many ligand molecules cannot be used effectively, because they do not differentiate between simple vascular permeability based uptake and true receptor binding. The development of methodologies which allow quantitative uptake of molecules in tumors is a primary focus of this grant in the renewal period. Fluorescence imaging of receptor activity in vivo is done using a novel Magnetic Resonance-guided Optical (MRgO) imaging instrument that is customized for small animals, with a primary focus on glioma tumor studies. The hardware and software sub- systems will be developed further to provide 4 layer volumetric data of fluorescence tomography guided by the MR data, and overlayed for visualization of the entire orthotopic tumor. The goal of this work is to analyze how molecular tracers of glioma tumors can be used to effectively quantify tumor receptor activity, in addition to vascular perfusion from contrast MRI. The small molecule epidermal growth factor (EGF) is used as a probe in conjunction with a non-specific fluorophore agent to show that ratiometric measurements of the uptake could lead to quantification of the bound EGF Receptor uptake. Glioma tumors that are microinvasive and therefore are not detectable with typical MR imaging can be detected with this new probe molecule, and the dual probe method will be used to show how MRgO imaging can provide a fundamentally new method to image this disease. The design of high and low affinity probes of difference molecular weights for ratiometric imaging is studied in the system with ex vivo validation, to confirm that the in vivo images are truly reflective of the tissue concentration levels. The project ends with the study of microinvasion and testing the detection of this spontaneously and in the setting of anti-vascular therapy. The grant focuses on the technology development, methodology development about how optical fluorescence can be added usefully to imaging science, with these two potential applications in cancer.
Molecular imaging of tumor receptor activity would allow the ability to visualize tumor function, as well as the structural features that are seen with MRI. In this grant, a novel MR-guided optical (MRgO) fluorescence imaging system is used to develop and study methodologies which will allow quantitative receptor imaging of glioma tumors.
|DSouza, Alisha V; Marra, Kayla; Gunn, Jason R et al. (2016) Optical tracer size differences allow quantitation of active pumping rate versus Stokes-Einstein diffusion in lymphatic transport. J Biomed Opt 21:100501|
|Elliott, Jonathan T; Marra, Kayla; Evans, Linton T et al. (2016) Simultaneous in vivo fluorescent markers for perfusion, protoporphyrin metabolism and EGFR expression for optically guided identification of orthotopic glioma. Clin Cancer Res :|
|Pogue, Brian W; Paulsen, Keith D; Samkoe, Kimberley S et al. (2016) Vision 20/20: Molecular-guided surgical oncology based upon tumor metabolism or immunologic phenotype: Technological pathways for point of care imaging and intervention. Med Phys 43:3143|
|Elliott, Jonathan T; Samkoe, Kimberley S; Davis, Scott C et al. (2016) Image-derived arterial input function for quantitative fluorescence imaging of receptor-drug binding in vivo. J Biophotonics 9:282-95|
|Andreozzi, Jacqueline M; Zhang, Rongxiao; Gladstone, David J et al. (2016) Cherenkov imaging method for rapid optimization of clinical treatment geometry in total skin electron beam therapy. Med Phys 43:993-1002|
|Holt, Robert W; Demers, Jennifer-Lynn H; Sexton, Kristian J et al. (2015) Tomography of epidermal growth factor receptor binding to fluorescent Affibody in vivo studied with magnetic resonance guided fluorescence recovery in varying orthotopic glioma sizes. J Biomed Opt 20:26001|
|DSouza, Alisha V; Lin, Huiyun; Gunn, Jason et al. (2015) Logarithmic intensity compression in fluorescence guided surgery applications. J Biomed Opt 20:80504|
|Zhang, Rongxiao; D'souza, Alisha V; Gunn, Jason R et al. (2015) Cherenkov-excited luminescence scanned imaging. Opt Lett 40:827-30|
|Zhang, Rongxiao; Andreozzi, Jacqueline M; Gladstone, David J et al. (2015) Cherenkoscopy based patient positioning validation and movement tracking during post-lumpectomy whole breast radiation therapy. Phys Med Biol 60:L1-14|
|Andreozzi, Jacqueline M; Zhang, Rongxiao; Glaser, Adam K et al. (2015) Camera selection for real-time in vivo radiation treatment verification systems using Cherenkov imaging. Med Phys 42:994-1004|
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