In this renewal application, we seek to integrate innovations of frequency-domain photon migration (FDPM) optical tomography within the Siemen's Inveon system for multi-modality optical, PET, and CT small animal imaging.
The specific aims of this proposed project are to:
The specific aims of this proposed project are to: (1) Adapt FDPM detection and illumination systems into the gantry of the Inveon CT which can be coupled into the Inveon PET for hybrid CT, PET, and NIR optical tomography;(2) Build an animal bed compatible for CT, PET, and NIR tomography which facilitates administration of anesthesia, maintenance of animal temperature, as well as EKG and respiratory gating;(3) Integrate FDPM data acquisition software and Transpire/BCM RTE-based optical tomography algorithms for determination of percent injected dose per gram of tissue (%ID/gm) for comparison to PET values;(4) Optimize and define NIR optical tomography performance with optical phantoms;and (5) Validate NIR optical tomography in the multi-modality imager using unique imaging agents in animal models of cancer. Once a functioning hybrid NIR optical tomography is optimized and performance metrics determined from phantom experiments, we propose to: (1) Co-inject 18F-fluorodeoxy-glucose ([18F]-FDG) and Li-Cor's IRDye800CW labeled to 2-deoxyglucose (IRDye. 800CW-2-deoxyglucose (2DG)) in animals with orthotopic tumors to compare %ID/gm computed from PET and optical tomography;(2) Compare 9-(4-[18F] fluoro-3-hydroxymethylbutyl) guanine ([18F]-FHBG) and optical analogs in animals with tumors stably transfected to express viral thymidine kinase (vTK) to quantify gene expression with PET and optical tomography with Dr. Charles Brunicardi of the Department of Surgery and Dr. Carlos Gonzales of Cyclotope, Inc;(3) Compare %ID/gm of dual labeled agents targeting HER2 in breast cancer, v3 in tumor angiogenesis, and interleukin-11 receptor alpha expressed in osteoblastic bone metastases in animal models;and (4) Quantify uptake of a peptide that (i) is dual-labeled with 64Cu-DOTA and Li-Cor's IRDye800CW and (ii) targets active matrix metalloproteases, MMP-2, and -9 in gated PET, CT, and NIR optical tomography studies of myocardial infarct and of lung cancer in transgenic mice.

Public Health Relevance

The ultimate objective of this work will be to develop a new small animal imaging modality to complement current techniques for quantitative, hybrid studies. The ultimate objective of this work will be to develop a new small animal imaging modality to complement current techniques for quantitative, hybrid studies using optical tomography based upon time-dependent techniques. If successful, the project will produce the first optical tomography platform which can be economically integrated within existing molecular and anatomical imaging modalities.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA135673-10
Application #
8118854
Study Section
Special Emphasis Panel (ZRG1-SBIB-S (50))
Program Officer
Zhang, Yantian
Project Start
2003-09-16
Project End
2013-07-31
Budget Start
2011-08-01
Budget End
2012-07-31
Support Year
10
Fiscal Year
2011
Total Cost
$300,700
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Type
Schools of Medicine
DUNS #
800771594
City
Houston
State
TX
Country
United States
Zip Code
77225
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Lu, Yujie; Darne, Chinmay D; Tan, I-Chih et al. (2013) In vivo imaging of orthotopic prostate cancer with far-red gene reporter fluorescence tomography and in vivo and ex vivo validation. J Biomed Opt 18:101305
Lu, Yujie; Darne, Chinmay D; Tan, I-Chih et al. (2013) Far-red fluorescence gene reporter tomography for determination of placement and viability of cell-based gene therapies. Opt Express 21:24129-38
Darne, Chinmay D; Lu, Yujie; Tan, I-Chih et al. (2012) A compact frequency-domain photon migration system for integration into commercial hybrid small animal imaging scanners for fluorescence tomography. Phys Med Biol 57:8135-52
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Lu, Yujie; Zhu, Banghe; Shen, Haiou et al. (2010) A parallel adaptive finite element simplified spherical harmonics approximation solver for frequency domain fluorescence molecular imaging. Phys Med Biol 55:4625-45
Olabisi, Ronke M; Lazard, Zawaunyka W; Franco, Christy L et al. (2010) Hydrogel microsphere encapsulation of a cell-based gene therapy system increases cell survival of injected cells, transgene expression, and bone volume in a model of heterotopic ossification. Tissue Eng Part A 16:3727-36
Sampath, Lakshmi; Kwon, Sunkuk; Hall, Mary A et al. (2010) Detection of Cancer Metastases with a Dual-labeled Near-Infrared/Positron Emission Tomography Imaging Agent. Transl Oncol 3:307-217

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