Emerging data from genomic and proteomic screens suggest that many diseases have unique molecular profiles which are defining and may serve as prognostic markers. One currently unmet need in molecular imaging is the development of techniques that will allow the simultaneous imaging of a small number of such targets (""""""""in vivo mini-arrays""""""""). Single gene alterations are insufficient to characterize most diseases; however, using many of today's clinical imaging tools, it is difficult to assess more than one molecular parameter at a time. A second unmet need is the separation of signal intensity modulation by physiological effects (perfusion) from molecular activities in humans, in whom heterogeneity of disease may be much greater than in well characterized and well controlled animal models. The goal of this grant is to develop a modular platform approach to address both of these issues and to extend previously developed macroscopic fluorescence imaging to true in vivo multi-channel imaging (MCI) in the near infrared. We have previously shown that the near infrared window (NIR) allows acquisition of multiple independent imaging channels, that a number of distinct molecularly selective reporters can be created for diverse diseases, and that in vivo multi-channel imaging (MCI) is feasible. The proposed research will address a number of critical questions and focus on novel probe design based on a modular three component system of carrier backbone, distinct peptide linkers for multiple selectivities, and fluorochromes for independent molecular reporting; optimization of imaging/analysis to extract the greatest amount of molecular imaging content; and validation of the multi-channel approach using diverse disease models.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB001872-04
Application #
7097909
Study Section
Special Emphasis Panel (ZRG1-F05 (50))
Program Officer
Zhang, Yantian
Project Start
2003-09-01
Project End
2008-07-31
Budget Start
2006-08-01
Budget End
2007-07-31
Support Year
4
Fiscal Year
2006
Total Cost
$420,574
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Sheth, Rahul A; Arellano, Ronald S; Uppot, Raul N et al. (2015) Prospective trial with optical molecular imaging for percutaneous interventions in focal hepatic lesions. Radiology 274:917-26
Mahmood, Umar (2014) 2014 SNMMI highlights lecture: Oncology. J Nucl Med 55:9N-24N
Hung, Kenneth E; Maricevich, Marco A; Richard, Larissa Georgeon et al. (2010) Development of a mouse model for sporadic and metastatic colon tumors and its use in assessing drug treatment. Proc Natl Acad Sci U S A 107:1565-70
Sheth, Rahul A; Maricevich, Marco; Mahmood, Umar (2010) In vivo optical molecular imaging of matrix metalloproteinase activity in abdominal aortic aneurysms correlates with treatment effects on growth rate. Atherosclerosis 212:181-7
Sheth, Rahul A; Mahmood, Umar (2010) Optical molecular imaging and its emerging role in colorectal cancer. Am J Physiol Gastrointest Liver Physiol 299:G807-20
Sheth, Rahul Anil; Upadhyay, Rabi; Stangenberg, Lars et al. (2009) Improved detection of ovarian cancer metastases by intraoperative quantitative fluorescence protease imaging in a pre-clinical model. Gynecol Oncol 112:616-22
Sheth, Rahul A; Tam, Jenny M; Maricevich, Marco A et al. (2009) Quantitative endovascular fluorescence-based molecular imaging through blood of arterial wall inflammation. Radiology 251:813-21
Kozloff, Kenneth M; Quinti, Luisa; Patntirapong, Somying et al. (2009) Non-invasive optical detection of cathepsin K-mediated fluorescence reveals osteoclast activity in vitro and in vivo. Bone 44:190-8
Stangenberg, Lars; Ellson, Chris; Cortez-Retamozo, Virna et al. (2009) Abrogation of antibody-induced arthritis in mice by a self-activating viridin prodrug and association with impaired neutrophil and endothelial cell function. Arthritis Rheum 60:2314-24
Sheth, Rahul A; Josephson, Lee; Mahmood, Umar (2009) Evaluation and clinically relevant applications of a fluorescent imaging analog to fluorodeoxyglucose positron emission tomography. J Biomed Opt 14:064014

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