In vivo imaging of neoplastic disease at early stages or as residual disease after therapy is difficult due to relatively low cell numbers, weak signals and previously insensitive detection methods. At late stages, functional changes are relevant to treatment but have been difficult to discern in vivo. In an interdisciplinary approach, the here assembled consortium of investigators will address these obstacles through the use of novel optical imaging strategies, and improvements to the more conventional imaging modalities of MRI, CT and SPECT. These will permit us to address questions pertaining to the genetics, physiology and therapy of neoplastic disease by monitoring both structural and functional changes in small animal models of cancer noninvasively and in real-time. The optical imaging system, developed by investigators in this core resource program, uses cells labeled with the genetic reporters, such as luciferase, which encode photoproteins that emit light which is detectable by highly-sensitive CCD-cameras from outside the animal's body. This enables us to observe as few as a thousand cells and perform in viva functional analyses. As such, examination of the cells' response to drugs and physiological stimuli can be assessed. State of the art MR imaging will be employed in conjunction with the optical methods, and in parallel, to complement and strengthen the analyses. To enhance detection sensitivity and resolution, engineering faculty will develop new adaptations to MRI, including a novel prepolarized system, to increase versatility. New micro-CT and micro-SPECT systems will be deployed for structural analyses and molecular detection, respectively, in animal models. We will modify reporter genes and contrast agents, assess gene expression in transgenic animals, determine the role of specific genes in the development and control of cancer, optimize optical detectors and apply state of the art MRI methods to small animal models. Furthermore, this multiple modality approach enables us to evaluate the efficacy of combination drug therapies and novel immune cell therapies in treating various types of tumor cells at different disease stages.
The specific aims of this application are aimed at increasing the capabilities of investigators in the molecular and cellular in vivo study of cancer, develop improved imaging technologies that push the limits of current bioimaging methods, introduce young investigators to state of the art imaging, and accelerate the in vivo quantitative evaluation of novel antineoplastic therapeutics. These goals will be met by generating a shared imaging research resource at Stanford University with the ability of spatiotemporal analyses of both structure and function in neoplastic disease models.
|Thorne, Stephen H; Liang, Wenchun; Sampath, Padma et al. (2010) Targeting localized immune suppression within the tumor through repeat cycles of immune cell-oncolytic virus combination therapy. Mol Ther 18:1698-705|
|Contag, Christopher H; Sikorski, Rachel; Negrin, Robert S et al. (2010) Definition of an enhanced immune cell therapy in mice that can target stem-like lymphoma cells. Cancer Res 70:9837-45|
|Hardy, Jonathan; Chu, Pauline; Contag, Christopher H (2009) Foci of Listeria monocytogenes persist in the bone marrow. Dis Model Mech 2:39-46|
|Creusot, Remi J; Yaghoubi, Shahriar S; Chang, Pearl et al. (2009) Lymphoid-tissue-specific homing of bone-marrow-derived dendritic cells. Blood 113:6638-47|
|Ren, Gang; Zhang, Rong; Liu, Zhe et al. (2009) A 2-helix small protein labeled with 68Ga for PET imaging of HER2 expression. J Nucl Med 50:1492-9|
|Dragulescu-Andrasi, Anca; Liang, Gaolin; Rao, Jianghong (2009) In vivo bioluminescence imaging of furin activity in breast cancer cells using bioluminogenic substrates. Bioconjug Chem 20:1660-6|
|Ray, Pritha; De, Abhijit; Patel, Manishkumar et al. (2008) Monitoring caspase-3 activation with a multimodality imaging sensor in living subjects. Clin Cancer Res 14:5801-9|
|Banaszynski, Laura A; Sellmyer, Mark A; Contag, Christopher H et al. (2008) Chemical control of protein stability and function in living mice. Nat Med 14:1123-7|
|Hickerson, Robyn P; Smith, Frances J D; Reeves, Robert E et al. (2008) Single-nucleotide-specific siRNA targeting in a dominant-negative skin model. J Invest Dermatol 128:594-605|
|Tseng, Jeffrey R; Kang, Keon Wook; Dandekar, Mangal et al. (2008) Preclinical efficacy of the c-Met inhibitor CE-355621 in a U87 MG mouse xenograft model evaluated by 18F-FDG small-animal PET. J Nucl Med 49:129-34|
Showing the most recent 10 out of 57 publications