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A target cell-specific activatable fluorescence probe for in vivo molecular imaging of cancer based on a self-quenched avidin-rhodamine conjugate.

Abstract
A target cell-specific activation strategy for improved molecular imaging of peritoneal implants has been proposed, in which fluorophores are activated only in living targeted cells. A current example of an activatable fluorophore is one that is normally self-quenched by attachment to a peptide backbone but which can be activated by specific proteases that degrade the peptide resulting in "dequenching." In this study, an alternate fluorescence activation strategy is proposed whereby self-quenching avidin-rhodamine X, which has affinity for lectin on cancer cells, is activated after endocytosis and degradation within the lysosome. Using this approach in a mouse model of peritoneal ovarian metastases, we document target-specific molecular imaging of submillimeter cancer nodules with minimal contamination by background signal. Cellular internalization of receptor-ligand pairs with subsequent activation of fluorescence via dequenching provides a generalizable and highly sensitive method of detecting cancer microfoci in vivo and has practical implications for assisting surgical and endoscopic procedures.
AuthorsYukihiro Hama, Yasuteru Urano, Yoshinori Koyama, Mako Kamiya, Marcelino Bernardo, Ronald S Paik, In Soo Shin, Chang H Paik, Peter L Choyke, Hisataka Kobayashi
JournalCancer research (Cancer Res) Vol. 67 Issue 6 Pg. 2791-9 (Mar 15 2007) ISSN: 0008-5472 [Print] United States
PMID17363601 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)
Chemical References
  • Detergents
  • Fluorescent Dyes
  • Rhodamines
  • Avidin
Topics
  • Animals
  • Avidin (chemistry, pharmacokinetics)
  • Cell Line, Tumor
  • Detergents (chemistry)
  • Female
  • Fluorescence
  • Fluorescent Dyes (chemistry, pharmacokinetics)
  • Humans
  • Image Processing, Computer-Assisted
  • Mice
  • Ovarian Neoplasms (metabolism, pathology)
  • Rhodamines (chemistry, pharmacokinetics)
  • Spectrometry, Fluorescence

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