About TCRT

TCRT has been on continuous publication since 2002. It is covered currently by all the major data systems such as Medline, PubMed, Web of Science, Thomson's ISI and SCI and Scopus.

The 2012 Impact factor for TCRT is 1.943

TCRT Open Access
TCRT seeks original articles
Cancer Watch

Using In-Vivo Fluorescence Imaging in Personalized Cancer Diagnostics and Therapy, an Image and Treat Paradigm (549-560)

The major goal in developing drugs targeting specific tumor receptors, such as Monoclonal AntiBodies (MAB), is to make a drug compound that targets selectively the cancer-causing biomarkers, inhibits their functionality, and/or delivers the toxin specifically to the malignant cells. Recent advances in MABs show that their efficacy depends strongly on characterization of tumor biomarkers. Therefore, one of the main tasks in cancer diagnostics and treatment is to develop non-invasive in-vivo imaging techniques for detection of cancer biomarkers and monitoring their down regulation during the treatment. Such methods can potentially result in a new imaging and treatment paradigm for cancer therapy. In this article we have reviewed fluorescence imaging approaches, including those developed in our group, to detect and monitor Human Epidermal Growth Factor 2 (HER2) receptors before and during therapy. Transition of these techniques from the bench to bedside is the ultimate goal of our project. Similar approaches can be used potentially for characterization of other cancer related cell biomarkers.

Key words: Fluorescence imaging; Near infrared optical imaging; Targeted fluorescent probe; Affibody; Cancer treatment; Cancer diagnostics; Human epidermal growth factor receptor.

This article can be cited as:
Ardeshirpour, Y., Chernomordik, V., Capala, J., Hassan, M., Zielinsky, R., Griffiths, G., Achilefu, S., Smith, P., Gandjbakhche, A. Using In-Vivo Fluorescence Imaging in Personalized Cancer Diagnostics and Therapy, an Image and Treat Paradigm Technol Cancer Res Treat. 10, 549-560 (2011). DOI: 10.7785/tcrt.2012.500221


1.Nelson, A. L., Dhimolea, E., Reichert, J. M. Development trends for human monoclonal antibody therapeutics. Nature Reviews Drug Discovery 9, 767-774 (2010). [Crossref]
2. Reichert, J. M. Monoclonal antibodies as innovative therapeutics. Curr Pharm Biotechnol 9, 423-430 (2008). [Crossref]
3. Reichert, J. M. Antibodies to watch in 2010. MAbs 2, 84-100 (2010).
4. Adams, G. P., Weiner, L. M. Monoclonal antibody therapy of cancer. Nat Biotechnol 23, 1147 (2005).
5. Hynes, N. E., Lane, H. A. ERBBreceptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer 5, 341 (2005). [Crossref]
6. Laudadio, J., Quigley, D. I., Tubbs, R., Wolff, D. J. HER2 testing: a review of detection methodologies and their clinical performance. Expert Rev Mol Diagn 7, 53 (2007). [Crossref]
7. Moelans, C. B., de Weger, R. A., Van der Wall, E., van Diest, P. J. Current technologies for HER2 testing in breast cancer. Crit Rev Oncol Hematol, In Press. [Crossref]
8. Phillips, K. A., Marshall, D. A., Haas, J. S., Elkin, E. B., Liang, S. Y., Hassett, M., Ferrusi, I., Brock, J. E., Van Bebber, S. L. Clinical practice patterns and cost effectiveness of human epidermal growth receptor 2 testing strategies in breast cancer patients. Cancer 115, 5166-5174 (2009). [Crossref]
9. Escobedo, J. O., Rusin, O., Lim, S., Strongin, R. M. NIR dyes for bioimaging applications. Current Opinion in Chemical Biology 14, 64-70 (2010). [Crossref]
10. Hoffman, R. M. The multiple uses of fluorescent proteins to visualize cancer in vivo. NatRevCancer 5, 796-806 (2005). [Crossref]
11. Frangioni, J. V. In vivo near-infrared fluorescence imaging. Curr Opin Chem Bio 7, 626-34 (2003).
12. Graves, E. E., Weissleder, R., Ntziachristos, V. Fluorescence molecular imaging of small animal tumor models. CurrMol Med 4, 419-30 (2004). [Crossref]
13. Leblond, F., Davis, S. C., Valdes, P. A., Pogue, B. W. Pre-clinical whole-body fluorescence imaging: Review of instruments, methods and applications. Journal of Photochemistry & Photobiology B-Biology 98, 77-94 (2010). [Crossref]
14. Corlu, A., Choe, R., Durduran, T., Rosen, M. A., Schweiger, M., Arridge, S. R., Schnall, M. D., Yodh, A. G. Three-dimensional in vivo fluorescence diffuse optical tomography of breast cancer in humans. Optics Express 15, 6696-6716 (2007). [Crossref]
15. Montet, X., Ntziachristos, V., Grimm, J., Weissleder, R. Tomographic fluorescence mapping of tumor targets. Cancer Res 65, 6330-6 (2005). [Crossref]
16. Choe, R., Corlu, A., Lee, K., Durduran, T., Konecky, S. D., Grosicka-Koptyra, M., Arridge, S. R., Czerniecki, B. J., Fraker, D. L., DeMichele, A., Chance, B., Rosen, M. A., Yodh, A. G. Diffuse optical tomography of breast cancer during neoadjuvant chemotherapy: a case study with comparison to MRI. Med Phys 32, 1128-39 (2005). [Crossref]
17. Becker, A., Hessenius, C., Licha, K., Ebert, B., Sukowski, U., Semmler, W., Wiedenmann, B., Grotzinger, C. Receptor-targeted optical imaging of tumors with near-infrared fluorescent ligands. Nat Biotechnol 19, 327-31 (2001). [Crossref]
18. Slamon, D. J., Clark, G. M., Wong, S. G., Levin, W. J., Ullrich, A., McGuire. W. L. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235, 177 (1987).
19. Witton, C. J., Reeves, J. R., Going, J. J., Cooke, T. G., Bartlett, J. M. S. Expression of the HER1-4 family of receptor tyrosine kinases in breast cancer. J Pathol 200, 290 (2003). [Crossref]
20. Zidan, J., Dashkovsky, I., Stayerman, C., Basher, W., Cozacov, C., Hadary, A. Comparison of HER-2 overexpression in primary breast cancer and metastatic sites and its effect on biological targeting therapy of metastatic disease. Br J Cancer 93, 552 (2005).[Crossref]
21. Menard, S., Pupa, S. M., Campiglio, M., Tagliabue, E. Biologic and therapeutic role of HER2 in cancer. Oncogene 22, 6570-8 (2003).
22. Capala, J., Bouchelouche, K. Molecular imaging of HER2-positive breast cancer: a step toward an individualized ‘image and treat’ strategy. Curr Opin Oncol 22, 559-66 (2010). [Crossref]
23. Lee, S. B., Hassan, M., Fisher, R., Chertov, O., Chernomordik, V., Kramer-Marek, G., Gandjbakhche, A., Capala, J. Affibody molecules for in vivo characterization of HER2-positive tumors by near-infrared imaging. Clin Cancer Res 14, 3840-3849 (2008). [Crossref]
24. Nord, K., Gunneriusson, E., Ringdahl, J., Stahl, S., Uhlen, M., Nygren, P. A. Binding proteins selected from combinatorial libraries of an alpha-helical bacterial receptor domain. Nat Biotechnol 15, 772-7 (1997).
25. Lofblom, J., Feldwisch, J., Tolmachev, V., Carlsson, J., Stahl. S., Frejd, F. Y. Affibody molecules: engineered proteins for therapeutic, diagnostic, and biotechnological applications. FEBS J 277, 2670-2680 (2010). [Crossref]
26. Nygren, P. A. Alternative binding proteins: Affibody binding proteins developed from a small three-helix bundle scaffold. FEBS J 275, 2668-2676 (2008). [Crossref]
27. Tolmachev, V., Orlova, A., Nilsson, F. Y., Feldwisch, J., Wennborg, A., Abrahmsen, L. Affibody molecules: potential for in vivo imaging of molecular targets for cancer therapy. Expert Opin Biol Ther 7, 555 (2007). [Crossref]
28. Chernomordik, V., Hassan, M., Lee, S. B., Zielinski, R., Gandjbakhche, A., Capala, J. Quantitative analysis of HER2 receptors expression in vivo by near-infrared optical imaging. Molec Imag 9, 192-200 (2010). [Crossref]
29. Berezin, M. Y., Achilefu, S. Fluorescence lifetime measurements and biological imaging. Chem Rev 110, 2641-2684 (2010). [Crossref]
30. Szmacinski, H., Lakiwicz, J. R. in Topics in Fluorescence Spectroscopy. Lifetime-based Sensing (Plenum, New York) (1994).
31. Lakowics, J. R. Principles of Fluorescence Spectroscopy. 2nd ed. NewYork: Kluwer Academic/Plenum Publishers (1999).
32. Bloch, S., Lesage, F., McIntosh, L., Gandjbakhche, A., Liang, K., Achilefu, S. Whole-body fluorescence lifetime imaging of a tumor-targeted near-infrared molecular probe in mice. J Biomed Opt 10, 054003 (2005). [Crossref]
33. Gannot, I., Ron, I., Hekmat, F., Chernomordik, V., Gandjbakhche, A. Functional optical detection based on pH-dependent fluorescence lifetime. Lasers Surg Med 35, 342-348 (2004). [Crossref]
34. Griffiths, J. R. Are cancer cells acidic?. Br J Cancer 64, 425-427 (1991).
35. Soubret, A., Ripoll, J., Ntziachristos, V. Accuracy of fluorescent tomography in the presence of heterogeneities: study of the normalized Born ratio. IEEE Trans Image Process 24, 1377-1386 (2005). [Crossref]
36. Themelis, G., Yoo, J. S., Soh, K. S., Schulz, R., Ntziachristos, V. Real-time intraoperative fluorescence imaging system using light-absorption correction. J Biomed Opt 14, 064012 (2009). [Crossref]
37. Dunn, K. W., Sutton, T. A. Functional studies in living animals using multiphoton microscopy. ILAR J 49, 66-77 (2008).
38. Ntziachristos, V. Fluorescence molecular imaging. Annu Rev Biomed Eng  8, 1-33 (2006).
39. Chen, Y. C., Clegg, R. M. Fluorescence lifetime-resolved imaging. Photosynthesis Research 102, 143-155 (2010). [Crossref]
40. Becker, W. Advanced Time-correlated Single Photon Counting Techniques. Chemical physics, Berlin, Germany: Springer, 317-322 (2005). [Crossref]
41. Kumar, A. T. N., Raymond, S. B., Boverman, G., Boas, D. A., Bacskai, B. J. Time-resolved fluorescence tomography of turbid media based on lifetime contrast. Opt Express 14, 12255-12270 (2006).[Crossref]
42. Chernomordik, V., Gandjbakhche A. H., Hassan, M., Pajevic, S., Weiss, G. H. A CTRW-based model of time-resolved fluorescence lifetime imaging in a turbid medium. Optics Communications 283, 4832-4839 (2010). [Crossref]
43. Han, S. H., Farshchi-Heydari, S., Hall, D. J. Analytical Method for the fast time-domain reconstruction of fluorescent inclusions in vitro and in vivo. Biophys J 98, 350-357 (2010). [Crossref]
44. Kumar, A. T. N., Skoch, J., Bacskai, B. J., Boas, D. A., Dunn, A. K. Fluorescence-lifetime-based tomography for turbid media. Opt Lett 30, 3347 (2005).[Crossref]
45. Hattery, D., Chernomordik, V., Loew, M., Gannot, I., Gandjbakhche, A. Analytical Solutions for Time-Resolved Fluorescence Lifetime Imaging in a Turbid Medium Such as Tissue. JOSA(A) 18, 1523-1530 (2001).
46. Hall, D., Ma, G., Lesage, F., Wang, Y. Simple time-domain optical method for estimating the depth and concentration of a fluorescent inclusion in a turbid medium. Optics Lett 29, 2258-2260 (2004). [Crossref]
47. Nothdurft, R. E., Patwardhan, S. V., Akers, W., Ye, Y., Achilefu, S., Culver, J. P. In vivo fluorescence lifetime tomography, J Biomed Opt 14 (2009). [Crossref]
48. Godavarty, A., Sevick-Muraca, E. M., Eppstein, M. J. Three dimensional fluorescence lifetime tomography. Med Phys 32, 992-1000 (2005). [Crossref]
49. Oleary, M. A., Boas, D. A., Li, X. D., Chance, B., Yodh, A. G. Fluorescence lifetime imaging in turbid media. Opt Lett 21, 158-160 (1996).
50. McGinty, J, Tahir, K. R., Laine, R., Talbot, C. B., Dunsby, C., Neil, M. A. A., Quintana, L., French, P. M. W. Time-gated optical projection tomography. Journal of Biophotonics 1, 390-394 (2008).
51. Riley, J. D., Hassan, M., Chernomordik, V., Gannot, I., Gandjbakhche, A. H. Choice of data-types in time resolved fluorescence enhanced diffuse optical tomography. Medical Physics 34, 4890-900 (2007).[Crossref]
52. Hassan, M., Riley, J., Chernomordk, V., Smith, P., Pursley, R., Lee, S. B., Capala, J., Gandjbakhche, A. H. Fluorescence lifetime imaging system for in vivo studies. Molec Imag 6, 229-236 (2007).[Crossref]
53. Koenig, S., Riemann, I. High-resolution multiphoton tomography of human skin with subcellular spatial resolution and picosecond time resolution. J Biomed Opt 8, 432 (2003).[Crossref]
54. Nahta, R., Esteva, F. J. Herceptin: mechanisms of action and resistance. Cancer Lett 232, 123-38 (2006).
55. Willmann, J. K., van Bruggen, N., Dinkelborg, L. M., Gambhir, S. S. Molecular imaging in drug development. Nat Rev Drug Disc 7, 591-607 (2008). [Crossref]
56. Tokunaga, E., Oki, E., Nishida, K., Koga, T., Egashira, A., Morita, M., Kakeji Y., Maehara, Y. Trastuzumab and breast cancer: developments and current status. Int J Clin Oncol 11, 199-208 (2006). [Crossref]
57. Hassan, M., Chernomordik, V., Zielinski, R., Ardeshirpour, Y., Capala, J., Gandjbakhche A. In Vivo Method to Monitor Changes in HER2 Expression Using Near-Infrared Fluorescence Imaging. Molecular Imaging, In Press. [Crossref]
58. Zielinski, R., Lyakhov, I., Hassan, M., Kuban, M., Shafer-Weaver, K., Gandjbakhche, A., Capala, J. HER2-Affitoxin: A Potent Therapeutic Agent for the Treatment of HER2-Overexpressing Tumors. Clinical Cancer Research 17, 5071-5081 (2011). [Crossref]
59. http://www.fda.gov/ScienceResearch/SpecialTopics/CriticalPathInitiative/default.htm
60. http://www.fda.gov/downloads/ScienceResearch/SpecialTopics/CriticalPathInitiative/UCM186110.pdf
61. Kobayashi, H., Ogawa M., Alford R., Choyke P. L., Urano Y. New strategies for fluorescent probe design in medical diagnostic imaging. Chemical Reviews 110,  2620-2640 (2010). [Crossref]
62. Napp, J., Mathejczyk, J. E., Alves F. Optical imaging in vivo with a focus on paediatric disease: technical progress, current preclinical and clinical applications and future perspectives. Pediatric Radiology 41, 161-175 (2011). [Crossref]
63. Kelloff, G. J., Krohn, K. A., Larson, S. M., Weissleder, R., Mankoff, D. A., Hoffman, J. M., Link, J. M., Guyton, K. Z., Eckelman, W. C., Scher, H. I., O’Shaughnessy, J., Cheson, B. D., Sigman, C. C., Tatum, J. L., Mills, G. Q., Sullivan, D. C., Woodcock, J. The progress and promise of molecular imaging probes in oncologic drug development. Clinical Cancer Research 11, 7967-7985 (2005). [Crossref]
64. Rice, S. L., Roney, C. A., Daumar, P., Lewis, J. S. The next generation of positron emission tomography radiopharmaceuticals in oncology. Seminars in Nuclear Medicine 41, 265-282 (2011). [Crossref]
65. Kim, E., Park, S. B. Chemistry as a Prism: A Review of Light-Emitting Materials Having Tunable Emission Wavelength. Chemistry an Asian journal 4, 1646-1658 (2009). [Crossref]
66. Thayer, D., Unlu, M. B., Lin, Y., Yan, K., Nalcioglu, O., Gulsen, G. Dual-Contrast Dynamic MRI-DOT for Small Animal Imaging. Technology in Cancer Research and Treatment 9, 61-69 (2010).
67. Lebedev, A. Y., Cheprakov, A. V., Sakadzic´, S., Boas, D. A., Wilson, D. F., Vinogradov, S. A. Dendritic phosphorescent probes for oxygen imaging in biological systems. ACS Applied Materials & Interfaces 1, 1292-1304 (2009). [Crossref]
68. Apreleva, S. V., Wilson, D. F., Vinogradov, S. A. Tomographic imaging of oxygen by phosphorescence lifetime. Applied Optics 45, 8547-8559 (2006).[Crossref]
69. Schulz, R. B., Ale, A., Sarantopoulos, A., Freyer, M., Soehngen, E., Zientkowska, M., Ntziachristos, V. Hybrid System for Simultaneous Fluorescence and X-Ray Computed Tomography. IEEE Transactions on Medical Imaging 29, 465-473 (2010). [Crossref]
70. Razansky, D., Ntziachristos, V. Hybrid photoacoustic fluorescence molecular tomography using finite-element-based inversion. Medical Physics 34, 4293-4301 (2007). [Crossref]
71. Gruber, J. D., Paliwal, A., Krishnaswamy, V., Ghadyani, H., Jermyn, M., O’Hara, J. A., Davis, S. C., Kerley-Hamilton, J. S., Shworak, N. W., Maytin, E. V., Hasan, T., Pogue, B. W. System development for high frequency ultrasound-guided fluorescence quantification of skin ­layers. Journal of Biomedical Optics 15, 026028 (2010).
72. Davis, S. C., Pogue, B. W., Springett, R., Leussler, C., Mazurkewitz, P., Tuttle, S. B., Gibbs-Strauss, S. L., Jiang, S. S., Dehghani, H., Paulsen, K. D. Magnetic resonance-coupled fluorescence tomography scanner for molecular imaging of tissue. Review of Scientific Instruments 79, 064302 (2008). [Crossref]
73. Sampath, L., Kwon, S., Hall, M. A., Price, R. E., Sevick-Muraca, E. M. Detection of cancer metastases with a dual-labeled near- infrared/positron emission tomography imaging agent. Translational Oncology 3, 307-318 (2010).[Crossref]
74. Uchiyama, K., Ueno, M., Ozawa, S., Kiriyama, S., Shigekawa, Y., Yamaue, H. Combined Use of Contrast-Enhanced Intraoperative Ultrasonography and a Fluorescence Navigation System for Identifying Hepatic Metastases. World Journal of Surgery 34, 2953-2959 (2010). [Crossref]
75. Nahrendorf, M., Keliher, E., Marinelli, B., Waterman, P., Feruglio, P. F., Fexon, L., Pivovarov, M., Swirski, F. K., Pittet, M. J., Vinegoni, C., Weissleder, R. Hybrid PET-optical imaging using targeted probes. Proceedings of the National Academy of Sciences of the United States of America 107, 7910-7915 (2010).[Crossref]
76. Tan, Y., Jiang, H. DOT guided fluorescence molecular tomography of arbitrarily shaped objects. Med Physics 35, 5703-5707 (2008).[Crossref]
77. Lin, Y., Gao, H., Nalcioglu, O., Gulsen, G. Fluorescence diffuse optical tomography with functional and anatomical a priori information: feasibility study. Physics in Medicine and Biology 52, 5569-5585 (2007). [Crossref]
78. Lin, Y., Barber, W. C., Iwanczyk, J. S., Roeck, W., Nalcioglu, O., Gulsen, G. Quantitative fluorescence tomography using a combined tri-modality FT/DOT/XCT system. Optics Express 18, 7835-7850 (2010).
79. Brooksby, B., Pogue, B. W., Jiang, S. D., Dehghani, H., Srinivasan, S., Kogel, C., Tosteson, T. D., Weaver, J., Poplack, S. P., Paulsen, K. D. Imaging breast adipose and fibroglandular tissue molecular signatures by using hybrid MRI-guided near-infrared spectral tomography. Proceedings of the National Academy of Sciences of the United States of America 103, 8828-8833 (2006). [Crossref]

This article can be accessed at PubMed:

Purchase Downloadable Article

Corporate User


University/Academic User


Received: June 23, 2011; Revised: August 30, 2011; Accepted: October 6, 2011

TCRT December 2011

category image
Volume 10
No.6 (505-634)
December 2011
ISSN 1533-0338

DOI: 10.7785/tcrt.2012.500221

Yasaman Ardeshirpour, Ph.D.1
Victor Chernomordik, Ph.D.1
Jacek Capala, Ph.D.2
Moinuddin Hassan, Ph.D.1
Rafal Zielinsky, Ph.D.2
Gary Griffiths, Ph.D.3
Samuel Achilefu, Ph.D.4
Paul Smith, Ph.D.5
Amir Gandjbakhche, Ph.D.1*

1NIH/National Institute of Child Health and Human Development, Building 9, 9 Memorial Dr., Bethesda, MD 20892
2NIH/National Cancer Institute, Building 10-Magnuson Clinical Center, 10 Center Dr., Bethesda, MD 20892
3NIH/Imaging Probe Development Center, Building 9800, Medical Center Dr., Rockville, MD 20850
4Optical Radiology Lab, Department of Radiology, Washington University, 4525 Scott Avenue, St. Louis, MO 63110.
5NIH/National Institute of Biomedical Imaging and Bioengineering, Building 13, 3N18A 13 South Dr., Bethesda, MD 20892

*Corresponding author:
Amir Gandjbakhche, Ph.D.
E-mail: gandjbaa@mail.nih.gov