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Sensors for Proteolytic Activity Visualization and Their Application in Animal Models of Human Diseases

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Abstract

Various sensors designed for optical and photo(opto)acoustic imaging in living systems are becoming essential components of basic and applied biomedical research. Some of them including those developed for determining enzyme activity in vivo are becoming commercially available. These sensors can be used for various fluorescent signal detection methods: from whole body tomography to endoscopy with miniature cameras. Sensor molecules including enzyme-cleavable macromolecules carrying multiple quenched near-infrared fluorophores are able to deliver their payload in vivo and have long circulation time in bloodstream enabling detection of enzyme activity for extended periods of time at low doses of these sensors. In the future, more effective “activated” probes are expected to become available with optimized sensitivity to enzymatic activity, spectral characteristics suitable for intraoperative imaging of surgical field, biocompatibility and lack of immunogenicity and toxicity. New in vivo optical imaging methods such as the fluorescence lifetime and photo(opto)acoustic imaging will contribute to early diagnosis of human diseases. The use of sensors for in vivo optical imaging will include more extensive preclinical applications of experimental therapies. At the same time, the ongoing development and improvement of optical signal detectors as well as the availability of biologically inert and highly specific fluorescent probes will further contribute to the introduction of fluorescence imaging into the clinic.

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Abbreviations

ABP:

activity-based probe

AFI:

autofluorescence imaging

CPP:

cell-penetrating peptide

FITC:

fluorescein isothiocyanate

FMT:

fluorescence molecular tomography

ICG:

indocyanine green

MB:

methylene blue

MFS:

macromolecular fluorescent sensor

MMP:

matrix metalloproteinase

MPEG-gPLL:

methoxypolyethylene glycol-graft-poly(L-lysine) copolymer

NIR:

near-infrared

PSA:

prostate-specific antigen

qNIRF-ABP:

quenched near-infrared fluorescent activity-based probe

uPA:

urokinase-type plasminogen activator

References

  1. Moats, R. A., Fraser, S. E., and Meade, T. J. (1997) A “smart” magnetic resonance imaging agent that reports on specific enzymatic activity, Angewandte Chemie Int. Ed., 36, 726–731.

    Article  CAS  Google Scholar 

  2. Gambhir, S. S., Herschman, H. R., Cherry, S. R., Barrio, J. R., Satyamurthy, N., Toyokuni, T., Phelps, M. E., Larson, S. M., Balatoni, J., Finn, R., Sadelain, M., Tjuvajev, J., and Blasberg, R. (2000) Imaging transgene expression with radionuclide imaging technologies, Neoplasia, 2, 118–138.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Bennett, J. J., Tjuvajev, J., Johnson, P., Doubrovin, M., Akhurst, T., Malholtra, S., Hackman, T., Balatoni, J., Finn, R., Larson, S. M., Federoff, H., Blasberg, R., and Fong, Y. (2001) Positron emission tomography imaging for herpes virus infection: implications for oncolytic viral treat–ments of cancer, Nature Medicine, 7, 859–863.

    Article  CAS  PubMed  Google Scholar 

  4. Bogdanov, A. J., Matuszewski, L., Bremer, C., Petrovsky, A., and Weissleder, R. (2002) Oligomerization of paramagnetic substrates results in signal amplification and can be used for MR imaging of molecualr targets, Mol. Imaging, 1, 16–23.

    Article  CAS  PubMed  Google Scholar 

  5. Law, B., and Tung, C. H. (2009) Proteolysis: a biological process adapted in drug delivery, therapy, and imaging, Bioconj. Chem., 20, 1683–1695.

    Article  CAS  Google Scholar 

  6. Edgington, L., Verdoes, M., and Bogyo, M. (2011) Functional imaging of proteases: recent advances in the design and application of substrate–based and activity–based probes, Curr. Opin. Chem. Biol., 15, 798–805.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Pogue, B. W., Davis, S. C., Song, X., Brooksby, B. A., Dehghani, H., and Paulsen, K. D. (2006) Image analysis meth–ods for diffuse optical tomography, J. Biomed. Opt., 11, 33001.

    Article  PubMed  Google Scholar 

  8. Troyan, S. L., Kianzad, V., Gibbs–Strauss, S. L., Gioux, S., Matsui, A., Oketokoun, R., Ngo, L., Khamene, A., Azar, F., and Frangioni, J. V. (2009) The FLARE intraoperative near–infrared fluorescence imaging system: a first–in–human clinical trial in breast cancer sentinel lymph node mapping, Ann. Surg. Oncol., 16, 2943–2952.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Hutteman, M., van der Vorst, J. R., Mieog, J. S., Bonsing, B. A., Hartgrink, H. H., Kuppen, P. J., Lowik, C. W., Frangioni, J. V., van de Velde, C. J., and Vahrmeijer, A. L. (2011) Near–infrared fluorescence imaging in patients undergoing pancre–aticoduodenectomy, Eur. Surg. Res., 47, 90–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Boogerd, L. S., Handgraaf, H. J., Lam, H. D., Huurman, V. A., Farina–Sarasqueta, A., Frangioni, J. V., van de Velde, C. J., Braat, A. E., and Vahrmeijer, A. L. (2017) Laparoscopic detection and resection of occult liver tumors of multiple cancer types using real–time near–infrared fluo–rescence guidance, Surg. Endosc., 31, 952–961.

    Article  PubMed  Google Scholar 

  11. Mondal, S. B., Gao, S., Zhu, N., Liang, R., Gruev, V., and Achilefu, S. (2014) Real–time fluorescence image–guided oncologic surgery, Adv. Cancer Res., 124, 171–211.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Van der Vorst, J. R., Schaafsma, B. E., Verbeek, F. P., Keereweer, S., Jansen, J. C., van der Velden, L. A., Langeveld, A. P., Hutteman, M., Lowik, C. W., van de Velde, C. J., Frangioni, J. V., and Vahrmeijer, A. L. (2013) Near–infrared fluorescence sentinel lymph node mapping of the oral cavity in head and neck cancer patients, Oral Oncol., 49, 15–19.

    Article  PubMed  Google Scholar 

  13. Crane, L. M., Themelis, G., Pleijhuis, R. G., Harlaar, N. J., Sarantopoulos, A., Arts, H. J., van der Zee, A. G., Ntziachristos, V., and van Dam, G. M. (2011) Intraoperative multispectral fluorescence imaging for the detection of the sentinel lymph node in cervical cancer: a novel concept, Mol. Imaging Biol., 13, 1043–1049.

    Article  PubMed  Google Scholar 

  14. Cataldo, A. M., and Nixon, R. A. (1990) Enzymatically active lysosomal proteases are associated with amyloid deposits in Alzheimer brain, Proc. Natl. Acad. Sci. USA, 87, 3861–3865.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Edwards, D. R., and Murphy, G. (1998) Cancer. Proteases–invasion and more, Nature, 394, 527–528.

    Article  CAS  PubMed  Google Scholar 

  16. Fang, J., Shing, Y., Wiederschain, D., Yan, L., Butterfield, C., Jackson, G., Harper, J., Tamvakopoulos, G., and Moses, M. A. (2000) Matrix metalloproteinase–2 is required for the switch to the angiogenic phenotype in a tumor model, Proc. Natl. Acad. Sci. USA, 97, 3884–3889.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Murray, G. I., Duncan, M. E., O’Neil, P., Melvin, W. T., and Fothergill, J. E. (1996) Matrix metalloproteinase–1 is associated with poor prognosis in colorectal cancer, Nat. Med., 2, 461–462.

    Article  CAS  PubMed  Google Scholar 

  18. Chambers, A. F., and Matrisian, L. M. (1997) Changing views of the role of matrix metalloproteinases in metastasis, J. Natl. Cancer Inst., 89, 1260–1270.

    Article  CAS  PubMed  Google Scholar 

  19. Folkman, J. (1999) Angiogenic zip code, Nat. Biotechnol., 17, 749.

    Article  CAS  PubMed  Google Scholar 

  20. Davidson, B., Goldberg, I., Kopolovic, J., Lerner–Geva, L., Gotlieb, W. H., Ben–Baruch, G., and Reich, R. (1999) MMP–2 and TIMP–2 expression correlates with poor prog–nosis in cervical carcinoma–a clinicopathologic study using immunohistochemistry and mRNA in situ hybridiza–tion, Gynecol. Oncol., 73, 372–382.

    Article  CAS  PubMed  Google Scholar 

  21. Kanayama, H., Yokota, K., Kurokawa, Y., Murakami, Y., Nishitani, M., and Kagawa, S. (1998) Prognostic values of matrix metalloproteinase–2 and tissue inhibitor of metallopro–teinase–2 expression in bladder cancer, Cancer, 82, 1359–1366.

    Article  CAS  PubMed  Google Scholar 

  22. Sakakibara, M., Koizumi, S., Saikawa, Y., Wada, H., Ichihara, T., Sato, H., Horita, S., Mugishima, H., Kaneko, Y., and Koike, K. (1999) Membrane–type matrix metalloproteinase–1 expression and activation of gelatinase A as prognostic markers in advanced pediatric neuroblastoma, Cancer, 85, 231–239.

    Article  CAS  PubMed  Google Scholar 

  23. Shalinsky, D. R., Brekken, J., Zou, H., McDermott, C. D., Forsyth, P., Edwards, D., Margosiak, S., Bender, S., Truitt, G., Wood, A., Varki, N. M., and Appelt, K. (1999) Broad antitumor and antiangiogenic activities of AG3340, a potent and selective MMP inhibitor undergoing advanced oncology clinical trials, Ann. NY Acad. Sci., 878, 236–270.

    Article  CAS  PubMed  Google Scholar 

  24. Smith, H. W., and Marshall, C. J. (2010) Regulation of cell signalling by uPAR, Nat. Rev. Mol. Cell Biol., 11, 23–36.

    Article  CAS  PubMed  Google Scholar 

  25. Jedeszko, C., and Sloane, B. F. (2004) Cysteine cathepsins in human cancer, Biol. Chem., 385, 1017–1027.

    Article  CAS  PubMed  Google Scholar 

  26. Mohamed, M. M., and Sloane, B. F. (2006) Cysteine cathepsins: multifunctional enzymes in cancer, Nat. Rev. Cancer, 6, 764–775.

    Article  CAS  PubMed  Google Scholar 

  27. Keppler, D., Sameni, M., Moin, K., Mikkelsen, T., Diglio, C. A., and Sloane, B. F. (1996) Tumor progression and angio–genesis: cathepsin B & Co, Biochem. Cell Biol., 74, 799–810.

    Article  CAS  PubMed  Google Scholar 

  28. Foekens, J. A., Kos, J., Peters, H. A., Krasovec, M., Look, M. P., Cimerman, N., Meijer–van Gelder, M. E., Henzen–Logmans, S. C., van Putten, W. L., and Klijn, J. G. (1998) Prognostic significance of cathepsins B and L in primary human breast cancer, J. Clin. Oncol., 16, 1013–1021.

    Article  CAS  PubMed  Google Scholar 

  29. Harbeck, N., Alt, U., Berger, U., Kruger, A., Thomssen, C., Janicke, F., Hofler, H., Kates, R. E., and Schmitt, M. (2001) Prognostic impact of proteolytic factors (urokinase–type plas–minogen activator, plasminogen activator inhibitor 1, and cathepsins B, D, and L) in primary breast cancer reflects effects of adjuvant systemic therapy, Clin. Cancer Res., 7, 2757–2764.

    CAS  Google Scholar 

  30. Jagodic, M., Vrhovec, I., Borstnar, S., and Cufer, T. (2005) Prognostic and predictive value of cathepsins D and L in operable breast cancer patients, Neoplasma, 52, 1–9.

    CAS  PubMed  Google Scholar 

  31. Garcia, M., Platet, N., Liaudet, E., Laurent, V., Derocq, D., Brouillet, J. P., and Rochefort, H. (1996) Biological and clinical significance of cathepsin D in breast cancer metastasis, Stem Cells, 14, 642–650.

    Article  CAS  PubMed  Google Scholar 

  32. Macphee, C. H., Nelson, J. J., and Zalewski, A. (2005) Lipoprotein–associated phospholipase A2 as a target of therapy, Curr. Opin. Lipidol., 16, 442–446.

    Article  CAS  PubMed  Google Scholar 

  33. Fu, X., Kassim, S. Y., Parks, W. C., and Heinecke, J. W. (2001) Hypochlorous acid oxygenates the cysteine switch domain of pro–matrilysin (MMP–7). A mechanism for matrix metalloproteinase activation and atherosclerotic plaque rup–ture by myeloperoxidase, J. Biol. Chem., 276, 41279–41287.

    Article  CAS  PubMed  Google Scholar 

  34. Orlowski, R. Z. (2004) Bortezomib and its role in the man–agement of patients with multiple myeloma, Expert Rev. Anticancer Ther., 4, 171–179.

    Article  CAS  PubMed  Google Scholar 

  35. Evans, J. M., Donnelly, L. A., Emslie–Smith, A. M., Alessi, D. R., and Morris, A. D. (2005) Metformin and reduced risk of cancer in diabetic patients, Brit. Med. J., 330, 1304–1305.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Devy, L., Rabbani, S. A., Stochl, M., Ruskowski, M., Mackie, I., Naa, L., Toews, M., van Gool, R., Chen, J., Ley, A., Ladner, R. C., Dransfield, D. T., and Henderikx, P. (2007) PEGylated DX–1000: pharmacokinetics and antineoplastic activity of a specific plasmin inhibitor, Neoplasia, 9, 927–937.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Devy, L., Huang, L., Naa, L., Yanamandra, N., Pieters, H., Frans, N., Chang, E., Tao, Q., Vanhove, M., Lejeune, A., van Gool, R., Sexton, D. J., Kuang, G., Rank, D., Hogan, S., Pazmany, C., Ma, Y. L., Schoonbroodt, S., Nixon, A. E., Ladner, R. C., Hoet, R., Henderikx, P., Tenhoor, C., Rabbani, S. A., Valentino, M. L., Wood, C. R., and Dransfield, D. T. (2009) Selective inhibition of matrix metalloproteinase–14 blocks tumor growth, inva–sion, and angiogenesis, Cancer Res., 69, 1517–1526.

    Article  CAS  PubMed  Google Scholar 

  38. Burden, R. E., Gormley, J. A., Jaquin, T. J., Small, D. M., Quinn, D. J., Hegarty, S. M., Ward, C., Walker, B., Johnston, J. A., Olwill, S. A., and Scott, C. J. (2009) Antibody–mediat–ed inhibition of cathepsin S blocks colorectal tumor invasion and angiogenesis, Clin. Cancer Res., 15, 6042–6051.

    Article  CAS  PubMed  Google Scholar 

  39. Elie, B. T., Gocheva, V., Shree, T., Dalrymple, S. A., Holsinger, L. J., and Joyce, J. A. (2010) Identification and pre–clinical testing of a reversible cathepsin protease inhibitor reveals anti–tumor efficacy in a pancreatic cancer model, Biochimie, 92, 1618–1624.

    Article  CAS  PubMed  Google Scholar 

  40. Funovics, M., Weissleder, R., and Tung, C. H. (2003) Protease sensors for bioimaging, Anal. Bioanal. Chem., 377, 956–963.

    Article  CAS  PubMed  Google Scholar 

  41. Leblond, F., Davis, S. C., Valdes, P. A., and Pogue, B. W. (2010) Pre–clinical whole–body fluorescence imaging: review of instruments, methods and applications, J. Photochem. Photobiol. B, 98, 77–94.

    Article  CAS  PubMed  Google Scholar 

  42. Marshall, M. V., Rasmussen, J. C., Tan, I.–C., Aldrich, M. B., Adams, K. E., Wang, X., Fife, C. E., Maus, E. A., Smith, L. A., and Sevick–Muraca, E. M. (2010) Near–infrared fluorescence imaging in humans with indocyanine green: a review and update, Open Surg. Oncol. J., 2, 12–25.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Sevick–Muraca, E. M. (2012) Translation of near–infrared fluorescence imaging technologies: emerging clinical appli–cations, Annu. Rev. Med., 63, 217–231.

    Article  CAS  PubMed  Google Scholar 

  44. Stummer, W., Pichlmeier, U., Meinel, T., Wiestler, O. D., Zanella, F., and Reulen, H. J. (2006) Fluorescence–guided surgery with 5–aminolevulinic acid for resection of malig–nant glioma: a randomised controlled multicentre phase III trial, Lancet Oncol., 7, 392–401.

    Article  CAS  PubMed  Google Scholar 

  45. Feigl, G. C., Ritz, R., Moraes, M., Klein, J., Ramina, K., Gharabaghi, A., Krischek, B., Danz, S., Bornemann, A., Liebsch, M., and Tatagiba, M. S. (2010) Resection of malig–nant brain tumors in eloquent cortical areas: a new multi–modal approach combining 5–aminolevulinic acid and intraoperative monitoring, J. Neurosurg., 113, 352–357.

    Article  PubMed  Google Scholar 

  46. Lee, J., and Bogyo, M. (2010) Development of near–infrared fluorophore (NIRF)–labeled activity–based probes for in vivo imaging of legumain, ACS Chem. Biol., 5, 233–243.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Verdoes, M., Oresic Bender, K., Segal, E., van der Linden, W. A., Syed, S., Withana, N. P., Sanman, L. E., and Bogyo, M. (2013) Improved quenched fluorescent probe for imaging of cys–teine cathepsin activity, J. Am. Chem. Soc., 135, 14726–14730.

    Article  CAS  PubMed  Google Scholar 

  48. Bogdanov, A. A., and Mazzanti, M. L. (2013) Fluorescent macromolecular sensors of enzymatic activity for in vivo imaging, Prog. Mol. Biol. Transl., 113, 349–387.

    Article  CAS  Google Scholar 

  49. Yim, J. J., Tholen, M., Klaassen, A., Sorger, J., and Bogyo, M. (2018) Optimization of a protease activated probe for optical surgical navigation, Mol. Pharm., 15, 750–758.

    Article  CAS  PubMed  Google Scholar 

  50. Querol, M., and Bogdanov, A., Jr. (2006) Amplification strate–gies in MR imaging: activation and accumulation of sensing contrast agents (SCAs), J. Magn. Reson. Imaging, 24, 971–982.

    Article  PubMed  Google Scholar 

  51. Wadghiri, Y. Z., Hoang, D. M., Leporati, A., Gounis, M. J., Rodriguez–Rodriguez, A., Mazzanti, M. L., Weaver, J. P., Wakhloo, A. K., Caravan, P., and Bogdanov, A. A., Jr. (2018) High–resolution imaging of myeloperoxidase activity sensors in human cerebrovascular disease, Sci. Rep., 8, 7687.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Maeda, H., Ishida, N., Kawauchi, H., and Tsujimura, K. (1969) Reaction of fluorescein–isothiocyanate with proteins and amino acids. I. Covalent and non–covalent binding of fluorescein–isoth–iocyanate and fluorescein to proteins, J. Biochem., 65, 777–783.

    Article  CAS  PubMed  Google Scholar 

  53. French, T., So, P. T., Weaver, D. J., Jr., Coelho–Sampaio, T., Gratton, E., Voss, E. W., Jr., and Carrero, J. (1997) Two–pho–ton fluorescence lifetime imaging microscopy of macrophage–mediated antigen processing, J. Microsc., 185, 339–353.

    Article  CAS  PubMed  Google Scholar 

  54. Horino, K., Kindezelskii, A. L., Elner, V. M., Hughes, B. A., and Petty, H. R. (2001) Tumor cell invasion of model 3–dimensional matrices: demonstration of migratory pathways, collagen disrup–tion, and intercellular cooperation, FASEB J., 15, 932–939.

    Article  CAS  PubMed  Google Scholar 

  55. Bogdanov, A. A., Mazzanti, M., Castillo, G., and Bolotin, E. (2012) Protected graft copolymer (PGC) in imaging and therapy: a platform for the delivery of covalently and non–covalently bound drugs, Theranostics, 2, 553–576.

    Article  CAS  PubMed  Google Scholar 

  56. Weissleder, R., Tung, C. H., Mahmood, U., and Bogdanov, A., Jr. (1999) In vivo imaging of tumors with protease–activated near–infrared fluorescent probes, Nat. Biotechnol., 17, 375–378.

    Article  CAS  PubMed  Google Scholar 

  57. Mahmood, U., Tung, C. H., Bogdanov, A., Jr., and Weissleder, R. (1999) Near–infrared optical imaging of pro–tease activity for tumor detection, Radiology, 213, 866–870.

    Article  CAS  PubMed  Google Scholar 

  58. Ntziachristos, V., Tung, C. H., Bremer, C., and Weissleder, R. (2002) Fluorescence molecular tomography resolves protease activity in vivo, Nat. Med., 8, 757–760.

    Article  CAS  PubMed  Google Scholar 

  59. Bremer, C., Tung, C. H., Bogdanov, A., Jr., and Weissleder, R. (2002) Imaging of differential protease expression in breast cancers for detection of aggressive tumor pheno–types, Radiology, 222, 814–818.

    Article  PubMed  Google Scholar 

  60. Wunderbaldinger, P., Turetschek, K., and Bremer, C. (2003) Near–infrared fluorescence imaging of lymph nodes using a new enzyme sensing activatable macromolecular optical probe, Eur. Radiol., 13, 2206–2211.

    Article  PubMed  Google Scholar 

  61. Wunder, A., Tung, C. H., Muller–Ladner, U., Weissleder, R., and Mahmood, U. (2004) In vivo imaging of protease activity in arthritis: a novel approach for monitoring treat–ment response, Arthritis Rheum., 50, 2459–2465.

    Article  CAS  PubMed  Google Scholar 

  62. Lai, W. F., Chang, C. H., Tang, Y., Bronson, R., and Tung, C. H. (2004) Early diagnosis of osteoarthritis using cathep–sin B sensitive near–infrared fluorescent probes, Osteo–arthritis Cartilage, 12, 239–244.

    Article  Google Scholar 

  63. Chen, J., Tung, C. H., Mahmood, U., Ntziachristos, V., Gyurko, R., Fishman, M. C., Huang, P. L., and Weissleder, R. (2002) In vivo imaging of proteolytic activity in athero–sclerosis, Circulation, 105, 2766–2771.

    Article  PubMed  Google Scholar 

  64. Marten, K., Bremer, C., Khazaie, K., Sameni, M., Sloane, B., Tung, C. H., and Weissleder, R. (2002) Detection of dysplastic intestinal adenomas using enzyme–sensing molecular beacons in mice, Gastroenterology, 122, 406–414.

    Article  PubMed  Google Scholar 

  65. Goergen, C., Chen, H., Bogdanov, A. J., Sosnovik, D., and Kumar, A. (2012) In vivo fluorescence lifetime detection of an activatable probe in infarcted myocardium, J. Bomed. Optics, 17, 056001.

    Article  CAS  Google Scholar 

  66. Grimm, J., Kirsch, D. G., Windsor, S. D., Kim, C. F., Santiago, P. M., Ntziachristos, V., Jacks, T., and Weissleder, R. (2005) Use of gene expression profiling to direct in vivo molecular imaging of lung cancer, Proc. Natl. Acad. Sci. USA, 102, 14404–14409.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Nahrendorf, M., Sosnovik, D. E., Waterman, P., Swirski, F. K., Pande, A. N., Aikawa, E., Figueiredo, J. L., Pittet, M. J., and Weissleder, R. (2007) Dual channel optical tomo–graphic imaging of leukocyte recruitment and protease activity in the healing myocardial infarct, Circ. Res., 100, 1218–1225.

    Article  CAS  PubMed  Google Scholar 

  68. Alencar, H., Funovics, M. A., Figueiredo, J., Sawaya, H., Weissleder, R., and Mahmood, U. (2007) Colonic adenocar–cinomas: near–infrared microcatheter imaging of smart probes for early detection–study in mice, Radiology, 244, 232–238.

    Article  PubMed  Google Scholar 

  69. Ignat, M., Aprahamian, M., Lindner, V., Altmeyer, A., Perretta, S., Dallemagne, B., Mutter, D., and Marescaux, J. (2009) Feasibility and reliability of pancreatic cancer staging using fiberoptic confocal fluorescence microscopy in rats, Gastroenterology, 137, 1584–1592 e1581.

    Article  PubMed  Google Scholar 

  70. Ding, S., Blue, R. E., Moorefield, E., Yuan, H., and Lund, P. K. (2017) Ex vivo and in vivo noninvasive imaging of epi–dermal growth factor receptor inhibition on colon tumori–genesis using activatable near–infrared fluorescent probes, Mol. Imaging, 16, 1536012117729044.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Haller, J., Hyde, D., Deliolanis, N., de Kleine, R., Niedre, M., and Ntziachristos, V. (2008) Visualization of pul–monary inflammation using noninvasive fluorescence molecular imaging, J. Appl. Physiol., 104, 795–802.

    Article  CAS  PubMed  Google Scholar 

  72. Sheth, R. A., Upadhyay, R., Stangenberg, L., Sheth, R., Weissleder, R., and Mahmood, U. (2009) Improved detec–tion of ovarian cancer metastases by intraoperative quanti–tative fluorescence protease imaging in a pre–clinical model, Gynecol. Oncol., 112, 616–622.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Habibollahi, P., Figueiredo, J. L., Heidari, P., Dulak, A. M., Imamura, Y., Bass, A. J., Ogino, S., Chan, A. T., and Mahmood, U. (2012) Optical imaging with a cathepsin B activated probe for the enhanced detection of esophageal adenocarcinoma by dual channel fluorescent upper GI endoscopy, Theranostics, 2, 227–234.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Nahrendorf, M., Waterman, P., Thurber, G., Groves, K., Rajopadhye, M., Panizzi, P., Marinelli, B., Aikawa, E., Pittet, M. J., Swirski, F. K., and Weissleder, R. (2009) Hybrid in vivo FMT–CT imaging of protease activity in ath–erosclerosis with customized nanosensors, Arterioscler. Thromb. Vasc. Biol., 29, 1444–1451.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Blau, R., Epshtein, Y., Pisarevsky, E., Tiram, G., Israeli Dangoor, S., Yeini, E., Krivitsky, A., Eldar–Boock, A., Ben–Shushan, D., Gibori, H., Scomparin, A., Green, O., Ben–Nun, Y., Merquiol, E., Doron, H., Blum, G., Erez, N., Grossman, R., Ram, Z., Shabat, D., and Satchi–Fainaro, R. (2018) Image–guided surgery using near–infrared Turn–ON fluorescent nanoprobes for precise detection of tumor margins, Theranostics, 8, 3437–3460.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Tung, C. H., Mahmood, U., Bredow, S., and Weissleder, R. (2000) In vivo imaging of proteolytic enzyme activity using a novel molecular reporter, Cancer Res., 60, 4953–4958.

    CAS  PubMed  Google Scholar 

  77. Jaffer, F. A., Kim, D. E., Quinti, L., Tung, C. H., Aikawa, E., Pande, A. N., Kohler, R. H., Shi, G. P., Libby, P., and Weissleder, R. (2007) Optical visualization of cathepsin K activity in atherosclerosis with a novel, protease–activatable fluorescence sensor, Circulation, 115, 2292–2298.

    Article  CAS  PubMed  Google Scholar 

  78. Jaffer, F. A., Tung, C. H., Gerszten, R. E., and Weissleder, R. (2002) In vivo imaging of thrombin activity in experimental thrombi with thrombin–sensitive near–infrared molecular probe, Arterioscler. Thromb. Vasc. Biol., 22, 1929–1935.

    Article  CAS  PubMed  Google Scholar 

  79. Bremer, C., Tung, C. H., and Weissleder, R. (2001) In vivo molecular target assessment of matrix metalloproteinase inhibition, Nat. Med., 7, 743–748.

    Article  CAS  PubMed  Google Scholar 

  80. Lamfers, M. L., Gianni, D., Tung, C. H., Idema, S., Schagen, F. H., Carette, J. E., Quax, P. H., Van Beusechem, V. W., Vandertop, W. P., Dirven, C. M., Chiocca, E. A., and Gerritsen, W. R. (2005) Tissue inhibitor of metalloproteinase–3 expression from an oncolytic adenovirus inhibits matrix metalloproteinase activity in vivo without affecting antitumor efficacy in malignant glioma, Cancer Res., 65, 9398–9405.

    Article  CAS  PubMed  Google Scholar 

  81. Chen, J., Tung, C. H., Allport, J. R., Chen, S., Weissleder, R., and Huang, P. L. (2005) Near–infrared fluorescent imaging of matrix metalloproteinase activity after myocar–dial infarction, Circulation, 111, 1800–1805.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Deguchi, J. O., Aikawa, M., Tung, C. H., Aikawa, E., Kim, D. E., Ntziachristos, V., Weissleder, R., and Libby, P. (2006) Inflammation in atherosclerosis: visualizing matrix metallopro–teinase action in macrophages in vivo, Circulation, 114, 55–62.

    Article  PubMed  Google Scholar 

  83. Scherer, R. L., VanSaun, M. N., McIntyre, J. O., and Matrisian, L. M. (2008) Optical imaging of matrix metallo–proteinase–7 activity in vivo using a proteolytic nanobea–con, Mol. Imaging, 7, 118–131.

    Article  CAS  PubMed  Google Scholar 

  84. Klohs, J., Baeva, N., Steinbrink, J., Bourayou, R., Boettcher, C., Royl, G., Megow, D., Dirnagl, U., Priller, J., and Wunder, A. (2009) In vivo near–infrared fluorescence imaging of matrix metalloproteinase activity after cerebral ischemia, J. Cereb. Blood Flow Metab., 29, 1284–1292.

    Article  CAS  PubMed  Google Scholar 

  85. Messerli, S. M., Prabhakar, S., Tang, Y., Shah, K., Cortes, M. L., Murthy, V., Weissleder, R., Breakefield, X. O., and Tung, C. H. (2004) A novel method for imaging apoptosis using a caspase–1 near–infrared fluorescent probe, Neoplasia, 6, 95–105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Hsiao, J. K., Law, B., Weissleder, R., and Tung, C. H. (2006) In vivo imaging of tumor associated urokinase–type plasminogen activator activity, J. Biomed. Opt., 11, 34013.

    Article  CAS  PubMed  Google Scholar 

  87. Ho, G., Morin, J., Delaney, J., Cuneo, G., Yared, W., Rajopadhye, M., Peterson, J. D., and Kossodo, S. (2013) Detection and quantification of enzymatically active prostate–specific antigen in vivo, J. Biomed. Opt., 18, 101319.

    Article  CAS  PubMed  Google Scholar 

  88. Tung, C. H., Bredow, S., Mahmood, U., and Weissleder, R. (1999) Preparation of a cathepsin D sensitive near–infrared fluorescence probe for imaging, Bioconj. Chem., 10, 892–896.

    Article  CAS  Google Scholar 

  89. Bogdanov, A. A., Lin, C. P., Simonova, M., Matuszewski, L., and Weissleder, R. (2002) Cellular activation of the self–quenched fluorescent reporter probe in tumor microenvironment, Neoplasia, 4, 228–236.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Sloane, B. F., Yan, S., Podgorski, I., Linebaugh, B. E., Cher, M. L., Mai, J., Cavallo–Medved, D., Sameni, M., Dosescu, J., and Moin, K. (2005) Cathepsin B and tumor proteolysis: contribution of the tumor microenvironment, Semin. Cancer Biol., 15, 149–157.

    Article  CAS  PubMed  Google Scholar 

  91. Zhang, R., Brennan, M. L., Fu, X., Aviles, R. J., Pearce, G. L., Penn, M. S., Topol, E. J., Sprecher, D. L., and Hazen, S. L. (2001) Association between myeloperoxidase levels and risk of coronary artery disease, JAMA, 286, 2136–2142.

    Article  CAS  PubMed  Google Scholar 

  92. Hama, Y., Urano, Y., Koyama, Y., Kamiya, M., Bernardo, M., Paik, R. S., Shin, I. S., Paik, C. H., Choyke, P. L., and Kobayashi, H. (2007) A target cell–specific activatable flu–orescence probe for in vivo molecular imaging of cancer based on a self–quenched avidin–rhodamine conjugate, Cancer Res., 67, 2791–2799.

    Article  CAS  PubMed  Google Scholar 

  93. Hama, Y., Urano, Y., Koyama, Y., Gunn, A. J., Choyke, P. L., and Kobayashi, H. (2007) A self–quenched galac–tosamine–serum albumin–rhodamineX conjugate: a “smart” fluorescent molecular imaging probe synthesized with clinically applicable material for detecting peritoneal ovarian cancer metastases, Clin. Cancer Res., 13, 6335–6343.

    Article  CAS  PubMed  Google Scholar 

  94. Kedem, O., and Katchalsky, A. (1958) Thermodynamic analysis of the permeability of biological membranes to non–electrolytes, Biochim. Biophys. Acta, 27, 229–246.

    Article  CAS  PubMed  Google Scholar 

  95. Kumar, A. T. N., Rice, W. L., Lopez, J. C., Gupta, S., Goergen, C. J., and Bogdanov, A. A., Jr. (2016) Substrate–based near–infrared imaging sensors enable fluorescence lifetime contrast via built–in dynamic fluorescence quenching elements, ACS Sensors, 1, 427–436.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Blum, G., Weimer, R. M., Edgington, L. E., Adams, W., and Bogyo, M. (2009) Comparative assessment of substrates and activity based probes as tools for non–invasive optical imaging of cysteine protease activity, PLoS One, 4, e6374.

    Book  Google Scholar 

  97. Goergen, C. J., Chen, H. H., Bogdanov, A., Sosnovik, D. E., and Kumar, A. T. (2012) In vivo fluorescence lifetime detection of an activatable probe in infarcted myocardium, J. Biomed. Opt., 17, 056001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Olson, E. S., Aguilera, T. A., Jiang, T., Ellies, L. G., Nguyen, Q. T., Wong, E. H., Gross, L. A., and Tsien, R. Y. (2009) In vivo characterization of activatable cell penetrat–ing peptides for targeting protease activity in cancer, Integr. Biol. (Camb.), 1, 382–393.

    Article  CAS  PubMed Central  Google Scholar 

  99. Kato, D., Boatright, K. M., Berger, A. B., Nazif, T., Blum, G., Ryan, C., Chehade, K. A., Salvesen, G. S., and Bogyo, M. (2005) Activity–based probes that target diverse cys–teine protease families, Nat. Chem. Biol., 1, 33–38.

    Article  CAS  PubMed  Google Scholar 

  100. Blum, G., Mullins, S. R., Keren, K., Fonovic, M., Jedeszko, C., Rice, M. J., Sloane, B. F., and Bogyo, M. (2005) Dynamic imaging of protease activity with fluorescently quenched activ–ity–based probes, Nat. Chem. Biol., 1, 203–209.

    Article  CAS  PubMed  Google Scholar 

  101. Blum, G., von Degenfeld, G., Merchant, M. J., Blau, H. M., and Bogyo, M. (2007) Noninvasive optical imaging of cysteine protease activity using fluorescently quenched activity–based probes, Nat. Chem. Biol., 3, 668–677.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. University of Massachusetts Medical School, Department of Radiology, Laboratory of Molecular Imaging Probes, MA, 01655, Worcester, USA

    A. A. Bogdanov Jr.

  2. A. N. Bach Institute of Biochemistry, Federal Research Center “Fundamentals of Biotechnology”, Russian Academy of Sciences, Laboratory of Molecular Imaging, 119071, Moscow, Russia

    A. A. Bogdanov Jr., I. D. Solovyev & A. P. Savitsky

  3. Lomonosov Moscow State University, Faculty of Bioengineering and Bioinformatics, 119991, Moscow, Russia

    A. A. Bogdanov Jr.

  4. A. N. Bach Institute of Biochemistry, Fundamentals of Biotechnology Federal Research Center, Russian Academy of Sciences, Laboratory of Physical Biochemistry, 119071, Moscow, Russia

    I. D. Solovyev & A. P. Savitsky

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  1. A. A. Bogdanov Jr.
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  2. I. D. Solovyev
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  3. A. P. Savitsky
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Russian Text © A. A. Bogdanov, Jr., I. D. Solovyev, A. P. Savitsky, 2019, published in Uspekhi Biologicheskoi Khimii, 2019, Vol. 59, pp. 3–38.

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Bogdanov, A.A., Solovyev, I.D. & Savitsky, A.P. Sensors for Proteolytic Activity Visualization and Their Application in Animal Models of Human Diseases. Biochemistry Moscow 84 (Suppl 1), 1–18 (2019). https://doi.org/10.1134/S0006297919140013

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  • DOI: https://doi.org/10.1134/S0006297919140013

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