Proteinase Optical Imaging Tools for Cancer Detection and Response to Therapy

  • J. Oliver McIntyre
  • Lynn M. Matrisian


A variety of physiological processes such as wound healing and tissue remodeling are mediated by a plethora of proteinases – enzymes that can hydrolyze peptide bonds – of which as many as 622 have been identified in the human genome. These proteinases are classified into five of the seven clans of peptidases with known catalytic type: S (serine), C (cysteine), A (aspartyl), M (metallo), and T (threonine) [MEROPS,; (Rawlings et al. 2008) (Fig. 1)]. In many physiological processes, the proteinases mediate and/or regulate both intercellular signaling, such as in the release and/or processing of chemokines, and intracellular pathways, such as in the apoptotic pathways leading to programmed cell death. Dysregulation of the temporal and/or spatial co-ordination of these intracellular and/or intercellular pathways disrupts the normal physiology and rhythm of life that can be manifest in unregulated growth such as occurs in tumors and their metastatic progeny.


Reactive Functional Group Serine Hydrolase Proteolytic Cascade Hydrolyze Peptide Bond Optical Contrast Agent 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We thank Randy Scherer for the images of tumors and adenomas with proteolytic beacons. This work was supported by National Institutes of Health grant CA60867 to L.M.M., grant P30 068485 to the Vanderbilt-Ingram Cancer Center, and grant U24 CA126588, the Southeastern Center for Imaging Animal Models, Vanderbilt University Institute of Imaging Science.


  1. Achilefu, S. 2004. Lighting up tumors with receptor-specific optical molecular probes. Technology in Cancer Research and Treatment 3 (4):393–409.PubMedGoogle Scholar
  2. Achilefu, S., H. N. Jimenez, R. B. Dorshow, J. E. Bugaj, E. G. Webb, R. R. Wilhelm, R. Rajagopalan, J. Johler, and J. L. Erion. 2002. Synthesis, in vitro receptor binding, and in vivo evaluation of fluorescein and carbocyanine peptide-based optical contrast agents. Journal of Medicinal Chemistry 45 (10):2003–15.CrossRefPubMedGoogle Scholar
  3. Alencar, H., M. A. Funovics, J. Figueiredo, H. Sawaya, R. Weissleder, and U. Mahmood. 2007. Colonic adenocarcinomas: near-infrared microcatheter imaging of smart probes for early detection–study in mice. Radiology 244 (1):232–8.CrossRefPubMedGoogle Scholar
  4. Barrett, A. J., N. D. Rawlings, and J. F. Woessner, Jr. 1998. Handbook of Proteolytic Enzymes. London: Academic Press.Google Scholar
  5. Baruch, A., D. A. Jeffery, and M. Bogyo. 2004. Enzyme activity–it’s all about image. Trends in Cell Biology 14 (1):29–35.CrossRefPubMedGoogle Scholar
  6. Berger, D. H. 2002. Plasmin/plasminogen system in colorectal cancer. World Journal of Surgery 26 (7):767–771.CrossRefPubMedGoogle Scholar
  7. Blum, G., S. R. Mullins, K. Keren, M. Fonovic, C. Jedeszko, M. J. Rice, B. F. Sloane, and M. Bogyo. 2005. Dynamic imaging of protease activity with fluorescently quenched activity-based probes. Nature Chemical Biology 1 (4):203–9.CrossRefPubMedGoogle Scholar
  8. Blum, G., G. von Degenfeld, M. J. Merchant, H. M. Blau, and M. Bogyo. 2007. Noninvasive optical imaging of cysteine protease activity using fluorescently quenched activity-based probes. Nature Chemical Biology 3 (10):668–77.CrossRefPubMedGoogle Scholar
  9. Bremer, C., C. H. Tung, and R. Weissleder. 2001. In vivo molecular target assessment of matrix metalloproteinase inhibition. Nature Medicine 7 (6):743–8.CrossRefPubMedGoogle Scholar
  10. Brinckerhoff, C. E., and L. M. Matrisian. 2002. Matrix metalloproteinases: a tail of a frog that became a prince. Nature Reviews Molecular Cell Biology 3 (3):207–14.CrossRefPubMedGoogle Scholar
  11. Brindle, K. 2008. New approaches for imaging tumour responses to treatment. Nature Reviews Cancer 8 (2):94–107.CrossRefPubMedGoogle Scholar
  12. Bromme, D., and J. Kaleta. 2002. Thiol-dependent cathepsins: pathophysiological implications and recent advances in inhibitor design. Current Pharmaceutical Biotechnology 8 (18):1639–58.Google Scholar
  13. Caughey, G. H. 2007. Mast cell tryptases and chymases in inflammation and host defense. Immunological Reviews 217:141–54.CrossRefPubMedGoogle Scholar
  14. Chan, E. W., S. Chattopadhaya, R. C. Panicker, X. Huang, and S. Q. Yao. 2004. Developing photoactive affinity probes for proteomic profiling: hydroxamate-based probes for metalloproteases. Journal of the American Chemical Society 126 (44):14435–46.CrossRefPubMedGoogle Scholar
  15. Chance, B., S. Nioka, J. Zhang, E. F. Conant, E. Hwang, S. Briest, S. G. Orel, M. D. Schnall, and B. J. Czerniecki. 2005. Breast cancer detection based on incremental biochemical and physiological properties of breast cancers: a six-year, two-site study. Academic Radiology 12 (8):925–33.CrossRefPubMedGoogle Scholar
  16. Chen, Y., A. Gryshuk, S. Achilefu, T. Ohulchansky, W. Potter, T. Zhong, J. Morgan, B. Chance, P. N. Prasad, B. W. Henderson, A. Oseroff, and R. K. Pandey. 2005. A novel approach to a bifunctional photosensitizer for tumor imaging and phototherapy. Bioconjugate Chemistry 16 (5):1264–74.CrossRefPubMedGoogle Scholar
  17. Chen, W. T., and T. Kelly. 2003. Seprase complexes in cellular invasiveness. Cancer Metastasis Review 22 (2–3):259–69.CrossRefGoogle Scholar
  18. Chen, Y., G. Zheng, Z. H. Zhang, D. Blessington, M. Zhang, H. Li, Q. Liu, L. Zhou, X. Intes, S. Achilefu, and B. Chance. 2003. Metabolism-enhanced tumor localization by fluorescence imaging: in vivo animal studies. Optics Letters 28 (21):2070–72.CrossRefPubMedGoogle Scholar
  19. Coussens, L. M., B. Fingleton, and L. M. Matrisian. 2002. Matrix metalloproteinase inhibitors and cancer: trials and tribulations. Science 295 (5564):2387–92.CrossRefPubMedGoogle Scholar
  20. Coussens, L. M., and Z. Werb. 2002. Inflammation and cancer. Nature 420 (6917):860–7.CrossRefPubMedGoogle Scholar
  21. David, A., D. Steer, S. Bregant, L. Devel, A. Makaritis, F. Beau, A. Yiotakis, and V. Dive. 2007. Cross-linking yield variation of a potent matrix metalloproteinase photoaffinity probe and consequences for functional proteomics. Angewandte Chemie (International Ed. in English) 46 (18):3275–7.CrossRefGoogle Scholar
  22. Dive, V., Paulick, M., McIntyre, J.O., Matrisian, L.M., and Bogyo, M. 2008. Activity-based imaging and biochemical profiling tools for analysis of the cancer degradome. Edited by D. Edwards, The Cancer Degradome, New York: Springer Science.Google Scholar
  23. Duffy, M. J. 1996. Proteases as prognostic markers in cancer. Clinical Cancer Research 2 (4):613–18.PubMedGoogle Scholar
  24. Egeblad, M., and Z. Werb. 2002. New functions for the matrix metalloproteinases in cancer progression. Nature Reviews Cancer 2 (3):161–74.CrossRefPubMedGoogle Scholar
  25. Evans, M. J., and B. F. Cravatt. 2006. Mechanism-based profiling of enzyme families. Chemical Reviews 106 (8):3279–301.CrossRefPubMedGoogle Scholar
  26. Fonovic, M., and M. Bogyo. 2007. Activity based probes for proteases: applications to biomarker discovery, molecular imaging and drug screening. Current Pharmaceutical Design 13 (3):253–61.CrossRefPubMedGoogle Scholar
  27. Gross, J., and C. M. Lapiere. 1962. Collagenolytic activity in amphibian tissues: a tissue culture assay. Proceedings of the National Academy of Sciences of the United States of America 48:1014–1022.Google Scholar
  28. Herszenyi, L., M. Plebani, P. Carraro, M. De Paoli, G. Roveroni, R. Cardin, F. Foschia, Z. Tulassay, R. Naccarato, and F. Farinati. 2000. Proteases in gastrointestinal neoplastic diseases. Clinica Chimica Acta 291 (2):171–87.CrossRefGoogle Scholar
  29. Izmailova, E. S., N. Paz, H. Alencar, M. Chun, L. Schopf, M. Hepperle, J. H. Lane, G. Harriman, Y. Xu, T. Ocain, R. Weissleder, U. Mahmood, A. M. Healy, and B. Jaffee. 2007. Use of molecular imaging to quantify response to IKK-2 inhibitor treatment in murine arthritis. Arthritis and Rheumatism 56 (1):117–28.CrossRefPubMedGoogle Scholar
  30. Jaffer, F. A., P. Libby, and R. Weissleder. 2007. Molecular imaging of cardiovascular disease. Circulation 116 (9):1052–61.CrossRefPubMedGoogle Scholar
  31. Jeffery, D. A., and M. Bogyo. 2003. Chemical proteomics and its application to drug discovery. Current Opinion in Biotechnology 14 (1):87–95.CrossRefPubMedGoogle Scholar
  32. Jessani, N., M. Humphrey, W. H. McDonald, S. Niessen, K. Masuda, B. Gangadharan, J. R. Yates, 3rd, B. M. Mueller, and B. F. Cravatt. 2004. Carcinoma and stromal enzyme activity profiles associated with breast tumor growth in vivo. Proceedings of the National Academy of Sciences of the United States of America 101 (38):13756–61.Google Scholar
  33. Jessani, N., Y. Liu, M. Humphrey, and B. F. Cravatt. 2002. Enzyme activity profiles of the secreted and membrane proteome that depict cancer cell invasiveness. Proceedings of the National Academy of Sciences of the United States of America 99 (16):10335–40.Google Scholar
  34. Jiang, T., E. S. Olson, Q. T. Nguyen, M. Roy, P. A. Jennings, and R. Y. Tsien. 2004. Tumor imaging by means of proteolytic activation of cell-penetrating peptides. Proceedings of the National Academy of Sciences of the United States of America 101 (51):17867–72.Google Scholar
  35. Joyce, J. A., A. Baruch, K. Chehade, N. Meyer-Morse, E. Giraudo, F. Y. Tsai, D. C. Greenbaum, J. H. Hager, M. Bogyo, and D. Hanahan. 2004. Cathepsin cysteine proteases are effectors of invasive growth and angiogenesis during multistage tumorigenesis. Cancer Cell 5 (5):443–53.CrossRefPubMedGoogle Scholar
  36. Kato, D., K. M. Boatright, A. B. Berger, T. Nazif, G. Blum, C. Ryan, K. A. Chehade, G. S. Salvesen, and M. Bogyo. 2005. Activity-based probes that target diverse cysteine protease families. Nature Chemical Biology 1 (1):33–8.CrossRefPubMedGoogle Scholar
  37. Kelly, K. A., S. R. Setlur, R. Ross, R. Anbazhagan, P. Waterman, M. A. Rubin, and R. Weissleder. 2008. Detection of early prostate cancer using a hepsin-targeted imaging agent. Cancer Research 68 (7):2286–91.CrossRefPubMedGoogle Scholar
  38. Kerkela, E., R. Ala-aho, P. Klemi, S. Grenman, S. D. Shapiro, V. M. Kahari, and U. Saarialho-Kere. 2002. Metalloelastase (MMP-12) expression by tumour cells in squamous cell carcinoma of the vulva correlates with invasiveness, while that by macrophages predicts better outcome. Journal of Pathology 198 (2):258–69.CrossRefPubMedGoogle Scholar
  39. Koblinski, J. E., M. Ahram, and B. F. Sloane. 2000. Unraveling the role of proteases in cancer. Clinica Chimica Acta 291 (2):113–35.CrossRefGoogle Scholar
  40. Lauer-Fields, J. L., and G. B. Fields. 2002. Triple-helical peptide analysis of collagenolytic protease activity. Biological Chemistry 383 (7–8):1095–105.CrossRefPubMedGoogle Scholar
  41. Lauer-Fields, J. L., D. Minond, P. S. Chase, P. E. Baillargeon, S. A. Saldanha, R. Stawikowska, P. Hodder, and G. B. Fields. 2009. High throughput screening of potentially selective MMP-13 exosite inhibitors utilizing a triple-helical FRET substrate. Bioorganic & Medicinal Chemistry 17(3):990–1005.CrossRefGoogle Scholar
  42. Lecaille, F., J. Kaleta, and D. Bromme. 2002. Human and parasitic papain-like cysteine proteases: their role in physiology and pathology and recent developments in inhibitor design. Chemical Reviews 102 (12):4459–88.CrossRefPubMedGoogle Scholar
  43. Lepage, M., W. C. Dow, M. Melchior, Y. You, B. Fingleton, C. C. Quarles, C. Pepin, J. C. Gore, L. M. Matrisian, and J. O. McIntyre. 2007. Noninvasive detection of matrix metalloproteinase activity in vivo using a novel magnetic resonance imaging contrast agent with a solubility switch. Molecular Imaging 6 (6):393–403.PubMedGoogle Scholar
  44. Liotta, L. A., K. Tryggvason, S. Garbisa, I. Hart, C. M. Foltz, and S. Shafie. 1980. Metastatic potential correlates with enzymatic degradation of basement membrane collagen. Nature 284:67–8.CrossRefPubMedGoogle Scholar
  45. Lopez-Otin, C., and L. M. Matrisian. 2007. Emerging roles of proteases in tumour suppression. Nature Reviews Cancer 7 (10):800–8.CrossRefPubMedGoogle Scholar
  46. Lopez-Otin, C., and C. M. Overall. 2002. Protease degradomics: a new challenge for proteomics. Nature Reviews Molecular Cell Biology 3 (7):509–19.CrossRefPubMedGoogle Scholar
  47. Mahmood, U., and R. Weissleder. 2003. Near-infrared optical imaging of proteases in cancer. Molecular Cancer Therapeutics 2 (5):489–96.PubMedGoogle Scholar
  48. Marten, K., C. Bremer, K. Khazaie, M. Sameni, B. Sloane, C. H. Tung, and R. Weissleder. 2002. Detection of dysplastic intestinal adenomas using enzyme-sensing molecular beacons in mice. Gastroenterology 122 (2):406–14.CrossRefPubMedGoogle Scholar
  49. McIntyre, J. O., B. Fingleton, K. S. Wells, D. W. Piston, C. C. Lynch, S. Gautam, and L. M. Matrisian. 2004. Development of a novel fluorogenic proteolytic beacon for in vivo detection and imaging of tumour-associated matrix metalloproteinase-7 activity. Biochemical Journal 377 (Pt 3):617–28.PubMedGoogle Scholar
  50. McIntyre, J. O., and L. M. Matrisian. 2003. Molecular imaging of proteolytic activity in cancer. Journal of Cellular Biochemistry 90 (6):1087–97.CrossRefPubMedGoogle Scholar
  51. Melnikova, V., and M. Bar-Eli. 2007. Inflammation and melanoma growth and metastasis: the role of platelet-activating factor (PAF) and its receptor. Cancer Metastasis Reviews 26 (3–4):359–71.PubMedGoogle Scholar
  52. Minond, D., J. L. Lauer-Fields, M. Cudic, C. M. Overall, D. Pei, K. Brew, M. L. Moss, and G. B. Fields. 2007. Differentiation of secreted and membrane-type matrix metalloproteinase activities based on substitutions and interruptions of triple-helical sequences. Biochemistry 46 (12):3724–33.CrossRefPubMedGoogle Scholar
  53. Montet, X., J. L. Figueiredo, H. Alencar, V. Ntziachristos, U. Mahmood, and R. Weissleder. 2007. Tomographic fluorescence imaging of tumor vascular volume in mice. Radiology 242 (3):751–8.CrossRefPubMedGoogle Scholar
  54. Netzel-Arnett, S., J. D. Hooper, R. Szabo, E. L. Madison, J. P. Quigley, T. H. Bugge, and T. M. Antalis. 2003. Membrane anchored serine proteases: a rapidly expanding group of cell surface proteolytic enzymes with potential roles in cancer. Cancer Metastasis Review 22 (2–3):237–58.CrossRefGoogle Scholar
  55. Nioka, S., and B. Chance. 2005. NIR spectroscopic detection of breast cancer. Technology in Cancer Research and Treatment 4 (5):497–512.PubMedGoogle Scholar
  56. Ntziachristos, V., C. H. Tung, C. Bremer, and R. Weissleder. 2002. Fluorescence molecular tomography resolves protease activity in vivo. Nature Medicine 8 (7):757–60.CrossRefPubMedGoogle Scholar
  57. Orlowski, R. Z., and D. J. Kuhn. 2008. Proteasome inhibitors in cancer therapy: lessons from the first decade. Clinical Cancer Research 14 (6):1649–57.CrossRefPubMedGoogle Scholar
  58. Ovaa, H., B. M. Kessler, U. Rolen, P. J. Galardy, H. L. Ploegh, and M. G. Masucci. 2004. Activity-based ubiquitin-specific protease (USP) profiling of virus-infected and malignant human cells. Proceedings of the National Academy of Sciences of the United States of America 101 (8):2253–8.Google Scholar
  59. Overall, C. M., and R. A. Dean. 2006. Degradomics: systems biology of the protease web. Pleiotropic roles of MMPs in cancer. Cancer Metastasis Reviews 25 (1):69–75.CrossRefPubMedGoogle Scholar
  60. Pham, W., Y. Choi, R. Weissleder, and C. H. Tung. 2004. Developing a peptide-based near-infrared molecular probe for protease sensing. Bioconjugate Chemistry 15 (6):1403–7.CrossRefPubMedGoogle Scholar
  61. Powers, J. C., J. L. Asgian, O. D. Ekici, and K. E. James. 2002. Irreversible inhibitors of serine, cysteine, and threonine proteases. Chemical Reviews 102 (12):4639–750.CrossRefPubMedGoogle Scholar
  62. Rawlings, N. D., F. R. Morton, C. Y. Kok, J. Kong, and A. J. Barrett. 2008. MEROPS: the peptidase database. Nucleic Acids Research 36 (Database issue):D320–5.Google Scholar
  63. Rochefort, H., M. Garcia, M. Glondu, V. Laurent, E. Liaudet, J. M. Rey, and P. Roger. 2000. Cathepsin D in breast cancer: mechanisms and clinical applications, a 1999 overview. Clinica Chimica Acta 291 (2):157–70.CrossRefGoogle Scholar
  64. Rocks, N., G. Paulissen, M. El Hour, F. Quesada, C. Crahay, M. Gueders, J. M. Foidart, A. Noel, and D. Cataldo. 2008. Emerging roles of ADAM and ADAMTS metalloproteinases in cancer. Biochimie 90 (2):369–79.CrossRefPubMedGoogle Scholar
  65. Rudin, M., and R. Weissleder. 2003. Molecular imaging in drug discovery and development. Nature Reviews. Drug Discovery 2 (2):123–31.CrossRefPubMedGoogle Scholar
  66. Sadaghiani, A. M., S. H. Verhelst, and M. Bogyo. 2007a. Tagging and detection strategies for activity-based proteomics. Current Opinion in Chemical Biology 11 (1):20–8.CrossRefPubMedGoogle Scholar
  67. Sadaghiani, A. M., S. H. Verhelst, V. Gocheva, K. Hill, E. Majerova, S. Stinson, J. A. Joyce, and M. Bogyo. 2007b. Design, synthesis, and evaluation of in vivo potency and selectivity of epoxysuccinyl-based inhibitors of papain-family cysteine proteases. Chemical Biology 14 (5):499–511.CrossRefGoogle Scholar
  68. Saghatelian, A., N. Jessani, A. Joseph, M. Humphrey, and B. F. Cravatt. 2004. Activity-based probes for the proteomic profiling of metalloproteases. Proceedings of the National Academy of Sciences of the United States of America 101 (27):10000–5.Google Scholar
  69. Scherer, R. L., J. O. McIntyre, and L. M. Matrisian. 2008a. Imaging matrix metalloproteinases in cancer. Cancer Metastasis Reviews 27(4):679–690.Google Scholar
  70. Scherer, R. L., M. N. VanSaun, J. O. McIntyre, and L. M. Matrisian. 2008b. Optical imaging of matrix metalloproteinase-7 activity in vivo using a proteolytic nanobeacon. Molecular Imaging 7(3):118–131.PubMedGoogle Scholar
  71. Schmidinger, H., A. Hermetter, and R. Birner-Gruenberger. 2006. Activity-based proteomics: enzymatic activity profiling in complex proteomes. Amino Acids 30 (4):333–50.CrossRefPubMedGoogle Scholar
  72. Sica, A., P. Allavena, and A. Mantovani. 2008. Cancer related inflammation: the macrophage connection. Cancer Letters 267(2):204–215.Google Scholar
  73. Sieber, S. A., S. Niessen, H. S. Hoover, and B. F. Cravatt. 2006. Proteomic profiling of metalloprotease activities with cocktails of active-site probes. Nature Chemical Biology 2 (5):274–81.CrossRefPubMedGoogle Scholar
  74. Sloane, B. F., M. Sameni, I. Podgorski, D. Cavallo-Medved, and K. Moin. 2006. Functional imaging of tumor proteolysis. Annual Review of Pharmacology and Toxicology 46:301–15.CrossRefPubMedGoogle Scholar
  75. Speers, A. E., and B. F. Cravatt. 2004. Chemical strategies for activity-based proteomics. Chembiochem: A European Journal of Chemical Biology 5 (1):41–7.CrossRefGoogle Scholar
  76. Tsien, R. Y. 2005. Building and breeding molecules to spy on cells and tumors. FEBS Letters 579 (4):927–32.CrossRefPubMedGoogle Scholar
  77. Upadhyay, R., R. A. Sheth, R. Weissleder, and U. Mahmood. 2007. Quantitative real-time catheter-based fluorescence molecular imaging in mice. Radiology 245 (2):523–31.CrossRefPubMedGoogle Scholar
  78. Van de Wiele, C., and R. Oltenfreiter. 2006. Imaging probes targeting matrix metalloproteinases. Cancer Biotherapy & Radiopharmaceuticals 21 (5):409–17.CrossRefGoogle Scholar
  79. Vasiljeva, O., A. Papazoglou, A. Kruger, H. Brodoefel, M. Korovin, J. Deussing, N. Augustin, B. S. Nielsen, K. Almholt, M. Bogyo, C. Peters, and T. Reinheckel. 2006. Tumor cell-derived and macrophage-derived cathepsin B promotes progression and lung metastasis of mammary cancer. Cancer Research 66 (10):5242–50.CrossRefPubMedGoogle Scholar
  80. Weissleder, R., C. H. Tung, U. Mahmood, and A. Bogdanov, Jr. 1999. In vivo imaging of tumors with protease-activated near-infrared fluorescent probes. Nature Biotechnology 17 (4):375–8.CrossRefPubMedGoogle Scholar
  81. Weissleder, R., and V. Ntziachristos. 2003. Shedding light onto live molecular targets. Nature Medicine 9 (1):123–8.CrossRefPubMedGoogle Scholar
  82. Weissleder, R., and M. J. Pittet. 2008. Imaging in the era of molecular oncology. Nature 452 (7187):580–9.CrossRefPubMedGoogle Scholar
  83. Wilson, C. L., K. J. Heppner, P. A. Labosky, B. L. M. Hogan, and L. M. Matrisian. 1997. Intestinal tumorigenesis is suppressed in mice lacking the metalloproteinase matrilysin. Proceedings of the National Academy of Sciences of the United States of America 94 (4):1402–407.Google Scholar
  84. Witty, J. P., S. McDonnell, K. Newell, P. Cannon, M. Navre, R. Tressler, and L. M. Matrisian. 1994. Modulation of matrilysin levels in colon carcinoma cell lines affects tumorigenicity in vivo. Cancer Research 54:4805–12.PubMedGoogle Scholar
  85. Woessner, J. F., and H. Nagase. 2000. Matrix Metalloproteinases and TIMPs. New York: Oxford University Press Inc.Google Scholar
  86. Zheng, G., J. Chen, K. Stefflova, M. Jarvi, H. Li, and B. C. Wilson. 2007. Photodynamic molecular beacon as an activatable photosensitizer based on protease-controlled singlet oxygen quenching and activation. Proceedings of the National Academy of Sciences of the United States of America 104 (21):8989–94.Google Scholar
  87. Zhu, Q., E. B. Cronin, A. A. Currier, H. S. Vine, M. Huang, N. Chen, and C. Xu. 2005. Benign versus malignant breast masses: optical differentiation with US-guided optical imaging reconstruction. Radiology 237 (1):57–66.CrossRefPubMedGoogle Scholar
  88. Zuzak, K. J., M. D. Schaeberle, E. N. Lewis, and I. W. Levin. 2002. Visible reflectance hyperspectral imaging: characterization of a noninvasive, in vivo system for determining tissue perfusion. Analytical Chemistry 74 (9):2021–8.CrossRefPubMedGoogle Scholar

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Authors and Affiliations

  1. 1.Department of Cancer Biology, and Vanderbilt–Ingram Cancer Center and Vanderbilt University Institute of Imaging ScienceVanderbilt University, Medical CenterNashvilleUSA
  2. 2.Department of Cancer Biology, and Vanderbilt-Ingram Cancer CenterVanderbilt University Medical CenterNashvilleUSA

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