A target cell-specific activatable fluorescence probe for in vivo molecular imaging of cancer based on a self-quenched avidin-rhodamine conjugate.
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.
Hama
Yukihiro
Y
Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892-1088, USA.
Urano
Yasuteru
Y
Koyama
Yoshinori
Y
Kamiya
Mako
M
Bernardo
Marcelino
M
Paik
Ronald S
RS
Shin
In Soo
IS
Paik
Chang H
CH
Choyke
Peter L
PL
Kobayashi
Hisataka
H
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
D003902:Detergents; D005456:Fluorescent Dyes; D012235:Rhodamines; D001360:Avidin