There is a need to develop new agents and technologies to image and quantitate molecular signatures in vivo. The main rationale for this is two-fold: a) to allow the earlier detection of disease based on molecular abnormalities and b) to image specific biomarkers during treatment (e.g. the imaging of a protease duringprotease inhibitor treatment). In prior research we have a developed a number of""""""""smart"""""""" sensing optical molecular probes that change their fluorescent properties after target interaction. One of the main challenges so far has been to detect and quantitate these activatable molecular beacons in vivo. Based on an optical tomographic method we have now built the ftrst prototype small animal imaging system that is capable of detecting fluorescence activation in deep tissues (fluorescence mediated tomography, FMT). The overall goaJ of this application is to improve on the performance of this system, quantitate, validate and correlate the data and then expand the technology to more sophisticated and more sensitive measurements. During the R21 phase of the grant application (year 01), we will further optimize the system components of the prototype imaging system. During the subsequent R33 phase of the application, we will pursue the following aims: 1) design and build a larger source-detector array, higher sensitivity and lower noise FMT system, suited for whole-body and higher resolution imaging, and test it with appropriate mouse/molecular probes models; 2) integrate time-resolved technology into the FMT system to improve reconstructions and quantitation of fluorescence; 3) design an appropriate MR-compatible optical tomographic system. We will address the following clinically relevant questions: 1) can the technology be applied to detect the activation of molecular beacons in early/small tumors, 2).can the systems be used for quantitative measurements of specific enzymes in vitro and in vivo and 3) can the efficacy of protease inhibitors be imaged at the molecular level? The approach, if successful, is expected to have broad applications to a variety of novel biologic, immunologic, and molecular therapies designed to control and eradicate cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants Phase II (R33)
Project #
4R33CA091807-02
Application #
6711502
Study Section
Special Emphasis Panel (ZCA1-SRRB-D (O1))
Program Officer
Croft, Barbara
Project Start
2002-04-01
Project End
2006-03-31
Budget Start
2003-04-01
Budget End
2004-03-31
Support Year
2
Fiscal Year
2003
Total Cost
$630,677
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Haller, Jodi; Hyde, Damon; Deliolanis, Nikolaos et al. (2008) Visualization of pulmonary inflammation using noninvasive fluorescence molecular imaging. J Appl Physiol 104:795-802
Garofalakis, Anikitos; Zacharakis, Giannis; Meyer, Heiko et al. (2007) Three-dimensional in vivo imaging of green fluorescent protein-expressing T cells in mice with noncontact fluorescence molecular tomography. Mol Imaging 6:96-107
Meyer, Heiko; Garofalakis, Anikitos; Zacharakis, Giannis et al. (2007) Noncontact optical imaging in mice with full angular coverage and automatic surface extraction. Appl Opt 46:3617-27
Montet, Xavier; Figueiredo, Jose-Luiz; Alencar, Herlen et al. (2007) Tomographic fluorescence imaging of tumor vascular volume in mice. Radiology 242:751-8
Ntziachristos, Vasilis (2006) Fluorescence molecular imaging. Annu Rev Biomed Eng 8:1-33
Soubret, Antoine; Ntziachristos, Vasilis (2006) Fluorescence molecular tomography in the presence of background fluorescence. Phys Med Biol 51:3983-4001
Ntziachristos, Vasilis; Ripoll, Jorge; Wang, Lihong V et al. (2005) Looking and listening to light: the evolution of whole-body photonic imaging. Nat Biotechnol 23:313-20
Ripoll, Jorge; Ntziachristos, Vasilis (2005) Quantitative point source photoacoustic inversion formulas for scattering and absorbing media. Phys Rev E Stat Nonlin Soft Matter Phys 71:031912
Marias, Kostas; Ripoll, Jorge; Meyer, Heiko et al. (2005) Image analysis for assessing molecular activity changes in time-dependent geometries. IEEE Trans Med Imaging 24:894-900
Zacharakis, Giannis; Kambara, Hirokazu; Shih, Helen et al. (2005) Volumetric tomography of fluorescent proteins through small animals in vivo. Proc Natl Acad Sci U S A 102:18252-7

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