Abstract
One goal of molecular imaging is to establish a widely applicable technique for specific detection of tumors with minimal background originated from non-target tissues. In this study, a “smart” activatable strategy for specific tumor imaging is proposed in which pH-activatable targeted probes specifically detect tumors after binding to the target cell surface proteins, internalization, and eventual acidic pH activation within the acidic organelles. We successfully visualized submillimeter-sized tumors using this strategy in two different tumor mouse models. Since the design of pH-activatable targeted probes can be applied to any target molecules on the cell surface that are to be internalized after ligand binding, this imaging strategy can afford a general and powerful method to diagnose and monitor the target tumors.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Hengerer, A., Wunder, A., Wagenaar, D. J., Vija, A. H., Shah, M., and Grimm, J. (2005) From genomics to clinical molecular imaging. Proceedings of the IEEE 93, 819–828.
Krohn, K. A., O’Sullivan, F., Crowley, J., Eary, J. F., Linden, H. M., Link, J. M., Mankoff, D. A., Muzi, M., Rajendran, J. G., Spence, A. M., and Swanson, K. R. (2007) Challenges in clinical studies with multiple imaging probes. Nucl Med Biol 34, 879–885.
Becker, A., Hessenius, C., Licha, K., Ebert, B., Sukowski, U., Semmler, W., Wiedenmann, B., and Grotzinger, C. (2001) Receptor-targeted optical imaging of tumors with near-infrared fluorescent ligands. Nat Biotechnol 19, 327–331.
Moon, W. K., Lin, Y., O’Loughlin, T., Tang, Y., Kim, D. -E., Weissleder, R., and Tung, C. -H. (2003) Enhanced tumor detection using a folate receptor-targeted near-infrared fluorochrome conjugate. Bioconjug Chem 14, 539–545.
Weissleder, R., Tung, C. -H., Mahmood, U., and Bogdanov, A. (1999) In vivo imaging of tumors with protease-activated near-infrared fluorescent probes. Nat Biotechnol 17, 375–378.
Bremer, C., Tung, C. -H., and Weissleder, R. (2001) In vivo molecular target assessment of matrix metalloproteinase inhibition. Nat Med 7, 743–748.
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 fluorescence probe for in vivo molecular imaging of cancer based on a self-quenched avidin-rhodamine conjugate. Cancer Res 67, 2791–2799.
Kamiya, M., Kobayashi, H., Hama, Y., Koyama, Y., Bernardo, M., Nagano, T., Choyke, P. L., and Urano, Y. (2007) An enzymatically activated fluorescence probe for targeted tumor imaging. J Am Chem Soc 129, 3918–3929.
Hama, Y., Urano, Y., Koyama, Y., Choyke, P. L., and Kobayashi, H. (2006) Targeted optical imaging of cancer cells using lectin-binding BODIPY conjugated avidin. Biochem Biophys Res Commun 348, 807–813.
Austin, C. D., De Maziere, A. M., Pisacane, P. I., van Dijk, S. M., Eigenbrot, C., Sliwkowski, M. X., Klumperman, J., and Scheller, R. H. (2004) Endocytosis and sorting of ErbB2 and the site of action of cancer therapeutics trastuzumab and geldanamycin. Mol Biol Cell 15, 5268–5282.
Hongyan Li, Z. M. Q. (2002) Transferrin/transferrin receptor-mediated drug delivery. Med Res Rev 22, 225–250.
Konan, Y. N., Gurny, R., and Allemann, E. (2002) State of the art in the delivery of photosensitizers for photodynamic therapy. J Photochem Photobiol 66, 89–106.
Atobe, K., Ishida, T., Ishida, E., Hashimoto, K., Kobayashi, H., Yasuda, J., Aoki, T., Obata, K. -I., Kikuchi, H., Akita, H., Asai, T., Harashima, H., Oku, N., and Kiwada, H. (2007) In vitro efficacy of a sterically stabilized immunoliposomes targeted to membrane type 1 matrix metalloproteinase (MT1-MMP). Biol Pharm Bull 30, 972–978.
Urano, Y., Asanuma, D., Hama, Y., Koyama, Y., Barrett, T., Kamiya, M., Nagano, T., Watanabe, T., Hasegawa, A., Choyke, P. L., and Kobayashi, H. (2009). Selective molecular imaging of viable cancer cells with pH-activatable fluorescence probes. Nat Med 15(1): 104–109.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2009 Humana Press, a part of Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Asanuma, D., Kobayashi, H., Nagano, T., Urano, Y. (2009). Fluorescence Imaging of Tumors with “Smart” pH-Activatable Targeted Probes. In: Rich, P., Douillet, C. (eds) Bioluminescence. Methods in Molecular Biology™, vol 574. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60327-321-3_5
Download citation
DOI: https://doi.org/10.1007/978-1-60327-321-3_5
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-60327-320-6
Online ISBN: 978-1-60327-321-3
eBook Packages: Springer Protocols