title: 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.
authors.affiliation: Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892-1088, USA.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Hama
authors.forename: Yasuteru
authors.initials: Y
authors.lastname: Urano
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Koyama
authors.forename: Mako
authors.initials: M
authors.lastname: Kamiya
authors.forename: Marcelino
authors.initials: M
authors.lastname: Bernardo
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Paik
authors.forename: In Soo
authors.initials: IS
authors.lastname: Shin
authors.forename: Chang H
authors.initials: CH
authors.lastname: Paik
authors.forename: Peter L
authors.initials: PL
authors.lastname: Choyke
authors.forename: Hisataka
authors.initials: H
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D001360:Avidin / Q000737:chemistry / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D003902:Detergents / Q000737:chemistry; D005260:Female; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D051379:Mice; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D012235:Rhodamines / Q000737:chemistry / Q000493:pharmacokinetics*; D013050:Spectrometry, Fluorescence
chemical_list: D003902:Detergents; D005456:Fluorescent Dyes; D012235:Rhodamines; D001360:Avidin